Facially amphiphilic polymers as anti-infective agents

ABSTRACT

Facially amphiphilic polymers and articles made therefrom having biocidal surfaces are disclosed. The polymers can inhibit the growth of microorganisms in contact with the surface or in areas adjacent to said biocidal surface. There is also disclosed a method to identify and optimize the facial amphiphilicity of polyamide, polyester, polyurea, polyurethane, polycarbonate and polyphenylene polymers. Utility as a contact disinfectant is disclosed.

REFERENCE TO PREVIOUS APPLICATIONS

This application claims priority to U.S. Provisional Patent ApplicationSer. No. 60/274,145 filed Mar. 8, 2001.

GOVERNMENT SUPPORT

This invention was supported in part by funding from the U.S. Government(NSF Grant DMR00-79909) and the U.S. Government may therefore havecertain rights in the invention.

FIELD OF THE INVENTION

The present invention relates to the design and synthesis of faciallyamphiphilic polymeric compounds with microbiocidal properties that canbe coated on or incorporated into materials and methods to design thesame. The present invention further relates to methods to identify anddesign facially amphiphilic polymers and methods to prevent or limitmicrobial growth.

BACKGROUND OF THE INVENTION

Amphiphilic molecules exhibit distinct regions of polar and nonpolarcharacter. These regions can result from substitution of hydrophobic andhydrophilic substituents into specific and distinct regions ofconformationally defined molecules. Alternately a conformationallyflexible molecule or macromolecule can adopt an ordered structure inwhich the hydrophobic and hydrophilic substituents on the moleculesegregate to different areas or faces of the molecule. Commonlyoccurring amphiphilic molecules include surfactants, soaps, detergents,peptides, proteins and copolymers. These molecules have the capacity toself-assemble in appropriate solvents or at interfaces to form a varietyof amphiphilic structures. The size and shape of these structures varieswith the specific composition of the amphiphilic molecule and solventconditions such as pH, ionic strength and temperature.

Amphiphilic peptides with unique broad-spectrum antimicrobial propertieshave been isolated from a variety of natural sources including plants,frogs, moths, silk worms, pigs and humans (H. G. Boman Immunol Rev. 2000173:5–16; R. E. Hancock and R. Lehrer, Trends Biotechnol. 199816:82–88). These compounds include the magainin 1 (1) and dermaseptin S1(2) isolated from the skin of frogs and the cecropin A (3) isolated fromthe cecropia moth. These naturally occurring compounds havebroad-spectrum antibacterial activity and they do not appear prone tothe development of bacterial resistance. These compounds are relativelylow molecular weight peptides that have a propensity to adopt α-helicalconformation in hydrophobic media or near a hydrophobic surface and as aresult are facially amphiphilic (i.e., one-third to two-thirds of thecylinder generated by the helical peptide has hydrophobic side chainswhile the

GIGKFLHSAGKFGKAFVGEIMKS-CO₂H (1) ALWKTMLKKLGTMALHAGKAALGAAADTISQGTQ-CO₂H(2) KWKLFKKIEKVGQNIRDGIIKAGPAVAVVGQATQIAK-NH₂ (3) RGGRLCYCRRRFCVCVGR-NH₂(4)remainder has hydrophilic side chains. These hydrophilic side chains areprimarily positively-charged at neutral pH. Hydrophobic amino acidscompose 40–60% of the total number of residues in most anti-microbialpeptides. The selectivity of the amphiphilic peptides (e.g. for bacteriavs. human erythrocytes) depends on the overall hydrophobicity. Thebiological activity of thee compounds depend on the ratio of charged (c)to hydrophobic (h) residues. When the ratio is varied from 1:1 (c:h) to1:2 (c:h) peptides with more hydrophobic residues tend to be more activetoward erythrocyte membranes. The physiochemical properties rather thanthe presence of particular amino acids or the tertiary structure of theside chains. Related peptides have been isolated from mammals and theseanti-microbial peptides have been suggested to be an important componentof the innate immune response. (Gennaro, R. et al. Biopoylmers (PeptideScience) 2000, 55, 31).

These observations recently have been extended to peptides (β-peptides)comprised of β-amino acids. These non-natural polypeptide mimetics alsoare capable of adopting stable α-helical and β-sheet structures althoughthe precise geometries of these structure are different form thosegenerated by α-amino acid oligomers. However, appropriate positioning ofhydrophobic and hydrophilic residues results in amphiphilicconformations with similar antimicrobial properties. This furtherconfirms the importance of repeating periodicity of hydrophobic andhydrophilic groups vis-à-vis the precise amino acid sequence inproducing facial amphiphilic antimicrobial compounds. (D. Seebach and J.L. Matthews, Chem Commun. 1997 2105; Hamuro, Y., Schneider, J. P.,DeGrado, W. F., J. Am. Chem. Soc. 1999, 121, 12200–12201; D. H. Appellaet al., J. Am. Chem. Soc., 1999 121, 2309).

Secondary structures other than helices may also give rise toamphiphilic compounds. The protegrins (4) are a related series ofanti-microbial peptides. (J. Chen et al., Biopolymers (Peptide Science),2000 55 88) The presence of a pair of disulfide bonds between Cys⁶–Cys¹⁵and Cys⁸–Cys¹³ results in a monomeric amphiphilic anti-parallel β-sheetformed by the chain termini and linked by a β-turn. The amphiphilicβ-sheet conformation is essential for anti-microbial activity againstboth gram-positive and gram-negative bacteria.

The data related to anti-microbial peptides suggests that facialamphiphilicity, the alignment of polar (hydrophilic) and nonpolar(hydrophobic) side chains on opposite faces of a secondary structuralelement formed by the peptide backbone, and not amino acid sequence, anyparticular secondary/tertiary structure, chirality or receptorspecificity is responsible for their biological activity.

Suitably substituted polymers which lack polyamide linkages also arecapable of adopting amphiphilic conformations. Solid phase chemistrytechnology was utilized to synthesize a class of meta substitutedphenylacetylenes that fold into helical structures in appropriatesolvents (J. C. Nelson et al., Science 1997 277:1793–96; R. B. Prince etal., Angew. Chem. Int. Ed. 2000 39:228–231). These molecules contain anall hydrocarbon backbone with ethylene oxide side chains such that whenexposed to a polar solvent (acetonitrile), the backbone would collapseto minimize its contact with this polar solvent. As a result of the metasubstitution, the preferred folded conformation is helical. This helicalfolding is attributed to a “solvophobic” energy term; although, theimportance of favorable π—π aromatic interactions in the folded stateare also likely to be important. Furthermore, addition of a less polarsolvent (CHCl₃) results in an unfolding of the helical structuredemonstrating that this folding is reversible.

Regioregular polythiophenes (5 and 6) have been shown to adoptamphiphilic conformations in highly ordered π-stacked arrays withhydrophobic side chains on one side of the array and hydrophilic sidechains on the other side. These polymers form thin films useful in theconstruction of nanocircuits. (Bjørnholm et al., J. Am. Chem. Soc., 1998120, 7643) These materials would be facially amphiphilic as definedherein; however, no biological properties have reported for thesecompounds.

Antimicrobial peptides have been incorporated onto surfaces or bulkmaterials, with some retention of antimicrobial properties. Haynie andco-workers at DuPont have investigated the activity of Antibacterialpeptides have been covalently attached to solid surfaces (S. L. Haynieet al., Antimicrob Agents Chemother, 1995 39:301–7; S. Margel et al., JBiomed Mater Res, 1993, 27:1463–76). A variety of natural and de novodesigned peptides were synthesized and tested for activity while stillattached to the solid support. The activity of the peptides decreasedwhen attached to the solid support although the peptides retained theirbroad spectrum of activity. For example, a de novo designed peptidereferred to as E14LKK has a MBC (minimum bactericidal activity) of 31μg/ml in solution as opposed to 1.5 mg/ml when attached to a solid phasebead. The peptides were attached to the resin with a 2 to 6-carbon alkyllinker. The porosity of Pepsyn K, the resin used in the synthesis, issmall (0.1 to 0.2 μm) compared to the bacteria, so the microbes may beunable to penetrate into the interior of the resin. Thus the greatmajority of the peptide would not be available for binding to cells. Theantimicrobial activity did not arise from a soluble component; noleached or hydrolyzed peptide was observed and the soluble extracts wereinactive. These studies indicate quite convincingly that antimicrobialpeptides retain their activity even when attached to a solid support.However, there is a need to optimize the presentation of the peptides toincrease their potency.

Other antimicrobial polymeric materials have been reported which containchemical functionality known to be antimicrobial (J. C. Tiller et al.,Proc Natl Acad Sci U S A, 2001 98:5981–85). A large portion of this workuses chemical functions such as alkylated pyridinium derivatives, whichare known to be toxic to mammalian cells. The antibiotic ciprofloxacinhas been grafted into a degradable polymer backbone (G. L. Y. Woo, etal., Biomaterials 2000 21:1235–1246). The activity of this materialrelies on cleavage of the active component from the polymer backbone.

Anti-infective vinyl copolymers, wherein monomers with hydrophobic andhydrophilic side chains have been randomly polymerized to producepolymers with amphiphilic properties, have also been described recentlyW. H. Mandeville III et al. (U.S. Pat. No. 6,034,129). These materialsare produced by polymerization of hydrophobic and hydrophilic acrylatemonomers. Alternately, the hydrophobic side chain is derived from astyrene derivative which is copolymerized with a hydrophilic acrylatemonomer wherein an ionic group is linked to the carboxylic acid. Thesepolymers, however, have relatively random arrangements of polar andnonpolar groups and are not facially amphiphilic as defined herein.

An alternative method to make amphiphilic polymers is to produce blockcopolymers comprised of hydrophobic blocks (A) and hydrophilic blocks(B), commonly polypropyleneoxy and polyethylenoxy segments respectively,into A-B, A-B-A or similar copolymers. These copolymers also are notfacially amphiphilic as defined herein.

BRIEF DESCIRPTION OF FIGURES BRIEF DESCRIPTION OF THE DRAWINGS

Specific embodiments of the invention have been chosen for the purposeof illustration and description but are not intended in any way torestrict the scope of the invention. These embodiments are shown in theaccompanying drawings wherein:

In FIG. 1 there is shown a cartoon that depicts the separation ofhydrophobic and hydrophilic side chains onto opposite faces of thepolymer backbone.

In FIG. 2 there is shown the general structure of a facially amphiphilicpolyamide or polyester copolymer formulae I and II, representativemonomer units for aromatic polyamides, Ia and IIa, the tworepresentative monomer units for polyamides with both aromatic andaliphatic components, Ib and IIb.

In FIG. 3 there is shown the general structure of polyamides withextended linking groups between the monomers.

In FIG. 4 there is shown the general structure IV of a faciallyamphiphilic polyurea, polycarbonate and polyurethane copolymers andrepresentative monomer units IVa, IVb and IVc, respectively. Examples oftwo typical polyurea monomers are exemplified in IVd and IVe.

In FIG. 5 there is shown the complete structure of a faciallyamphiphilic polyamide IId and polyurethane IVf.

In FIG. 6 there is shown typical examples of ortho- and meta-phenylenefacially amphiphilic polymers XII and XIII respectively derived fromsalicylamide and anthranilimide.

In FIG. 7 there is shown the synthesis of substituted salicylic andanthranilic acid monomers of XII and XIII.

In FIG. 8 there is shown the synthesis of polyureas XIa–XIc.

In FIG. 9 there is shown antimicrobial data for polyamide and polyureaoligomers

In FIG. 10 there is shown antimicrobial data for polyamide oligomers ofgeneral formula VII.

In FIG. 11 there is shown the time course for antibacterial activity ofa polyurea oligomer.

SUMMARY OF THE INVENTION

One object of the invention is to provide new polymeric compounds withanti-microbial properties which can be applied to or dispersedthroughout devices, articles and surfaces and which are capable ofkilling microorganisms on contact, but leach into the environment moreslowly than traditional small molecule anti-microbials. The polymericmaterials may be deposited as a film on the surface of a substrate ormay be dispersed

throughout a substrate to provide an anti-microbial surface. Thepolymeric materials of the present invention are anti-microbial polymersthat are designed to possess amphiphilic properties in the presence ofmicrobial cell walls and to disrupt the membrane and kill the organism.The polymeric materials are further designed to have low toxicity tomammalian cells.

The facially amphiphilic polymers of the present invention are polyamideor polyester compounds of formulae I and II wherein x is O, NR³ or S, yis CO, CS or SO₂ and A and B are aromatic, heteroaromatic or aliphaticmoieties appropriately substituted with polar and nonpolar groups;polyurea, polycarbamate, or polycarbonates compounds of formulae IVwherein x and y are O, NR³ or S, z is CO, CS or SO₂ and A and B arearomatic, heteroaromatic or aliphatic moieties appropriately substitutedwith polar and nonpolar groups; and polyphenylene and heteroarylenecompounds of formula V wherein is either a single bond, double bond,triple bond or absent and A and B are aromatic, heteroaromatic moietiesappropriately substituted with polar and nonpolar groups. R, R¹ and R²are end groups appropriate for the specific polymer chain and theirdesign is well know in the polymer art.

These facially amphiphilic polymers are capable of adopting repeatingsecondary structural motifs that allow for the segregation of polar andnonpolar regions of the molecule into different spatial regions. Theanti-microbial polymers adopt amphiphilic conformations when placed incontact with the cell walls of microorganisms and the amphiphilicmolecules are capable of disrupting essential cell wall functionsresulting in the death of the microorganism.

The present invention further provides methods for killing microorganismon surfaces by disposing thereon a facially amphiphilic polymer. Themethod for making compositions incorporating the facially amphiphilicpolymers includes providing a solution dispersion or suspension of thepolymer and applying it to the surface. Alternately compositions can beprepared by incorporating the polymer into plastics that subsequentlyare molded, shaped or extruded into other articles. The optimal methodto deliver the polymer will depend on several factors including thedesired coating thickness and the nature and configuration of thesubstrate and the physical characteristics of the facially amphiphilicpolymer.

The facially amphiphilic polymers of the present invention can have asubstantial range in molecular weight. Facially amphiphilic moleculeswith molecular weights of about 0.8 kD to about 20 kD will be more proneto leach from the surface of the substrate. The facially amphiphilicpolymer may be attached or immobilized on the substrate by anyappropriate method including covalent bonding, ionic interaction,coulombic interaction, hydrogen bonding or cross-linking. The polymersof the present invention provide a surface-mediated microbiocide thatonly kills organisms in contact with the surface. Moreover the polymersof the present invention are stable and retain their bioactivity forextended periods of time and are nontoxic to birds, fish, mammals andother higher organisms.

The present invention further provides a computational technique toevaluate the energy of polymer conformations and identify polymers whichhave the capability of exhibiting amphiphilic behavior and aid inidentifying optimal sites for substitution of polar and nonpolarsubstituents that confer amphiphilic properties.

DETAILED DESCRIPTION OF THE INVENTION

Microbial infections represent a serious continuing problem in human andanimal health. While amphiphilic α and β-peptides exhibit potentantibacterial, they are, nevertheless, difficult and expensive toprepare in large quantities. Peptides are sensitive to enzymatic andchemical hydrolysis. Exposure to microbial pathogens can occur in avariety of ways. Most objects encountered daily have the potential forharboring infectious organisms and new compounds and approaches forcontrolling the growth of microbes are extremely valuable and havesignificant commercial potential. Antimicrobial peptides related to themagainins have desirable biological activities but their utility islimited. An object the present invention is to provide new stableantimicrobial polymers which are available from inexpensive and readilyavailable monomers and which can be incorporated into, or on to, a widevariety of materials and can withstand chemical and enzymaticdegradation.

In recent years, the design of non-biological polymers with well-definedsecondary and tertiary structures (S. H. Gellman et al., Acc. Chem. Res.1998 31:173–80; A. E. Barron and R. N. Zuckerman, Curr. Opin. Chem.Biol., 1999 3:681–687; K. D. Stigers et al., Curr. Opin. Chem. Biol.,1999 3:714–723) has become an active area of research. One reason forthis interest is that for the first time, modem methods of solid phaseorganic chemistry (E. Atherton and R. C. Sheppard, Solid Phase PeptideSynthesis A Practical Approach IRL Press Oxford 1989) have allowed thesynthesis of homodisperse, sequence-specific oligomers with molecularweights approaching 5,000 Daltons. The development of this new field ofhomodisperse sequence-specific oligomers promises to generate moleculeswith novel chemical and physical properties that will span the gapbetween polymer and protein science. Polymers are statistical mixturesof molecules typically composed of one to a few monomers. By contrast,peptides and proteins are molecules typically composed from >15 monomerswith exact control over sequence, topology, and stereochemistry. Thesehomodisperse sequence-specific oligomers represent molecules withfeatures of both polymers and proteins.

Facially amphiphilic polymers can be homopolymers wherein one monomer issubstituted with both a nonpolar and a polar substituent or copolymerswherein one monomer is substituted with a polar substituent and theother monomer is substituted with a nonpolar substituent. Since theantimicrobial activity arises from the amphiphilic character conferredby a periodic pattern of side chains rather than the precise spatialarrangement of side chains, other substitution patterns are alsoexpected to produce facially amphiphilic polymers and they all areencompassed by the present invention. (see FIG. 7)

Polyamide and polyester homopolymers and copolymers of the presentinvention (FIG. 1) can be comprised solely of aromatic or heteroaromaticmonomers or may include both aromatic and aliphatic monomers. Oneembodiment of the invention is a copolymer with aromatic monomers andα-amino acid monomers. The polyamides and polyesters can be constructedeither by repetitively linking amino (or hydroxy) acid monomers (FIG. 1,I) or by alternating diamine (or dihydroxy) and dicarboxylic acidmonomers (FIG. 1, II). While the majority of aromatic rings in theexamples depicted in FIGS. 1 and 2 have a meta substitution pattern, oneskilled in the art would immediately appreciate that equivalent polymerscould be designed with an ortho or a para orientation and thesemodifications can alter the conformation and the physical properties ofthe resulting polymer. Furthermore although the copolymers in FIG. 1 Iaand Ila–IIc are depicted with one polar and one nonpolar substituent,other substitution patterns are equally plausible. The optimalsubstitution patterns are determined by the conformational properties ofthe polymer backbone.

While polyamides and polyesters are the most common occurring examplesof the present invention, other functional groups can be incorporatedinto the polymer backbone with similar results. In particular,thioamides and thioesters are anticipated to have very similarproperties. The distance between aromatic rings can significantly impactthe geometrical pattern of the polymer and this distance can be alteredby incorporating aliphatic chains of varying length (FIG. 1, IIc).Although IIc is depicted as a unsubstantiated alkylene chain, thealkylene chain can be optionally substituted or can comprise an aminoacid, a dicarboxylic acid or a diamine. The distance between and therelative orientation of monomers also can altered by replacing the amidebond with a surrogate with additional atoms (FIG. 2, XV–XVII). Thusreplacing the carbonyl group with a dicarbonyl alters the distancebetween the monomers and the propensity of dicarbonyl unit to adopt ananti arrangement of the two carbonyl moiety and alter the periodicity ofthe polymer. Pyromellitic anhydride (FIG. 2, IVg) represents stillanother alternative to simple amide linkages which can significant alterthe conformation and physical properties of the copolymer (FIG. 1, IVb).

The synthetic processes can be modified to produce different ranges inmolecular weight and the anti-microbial polymer of the present inventionwill have a molecular weight selected to impart physical and chemicalproperties optimized for the particular application being contemplated.Traditional polymer syntheses produce a product with a range ofmolecular weights. The polymer chemist will readily appreciate that thechain length of these polymers can be varied by techniques know in thepolymer art. Polymers of the present invention can range in molecularweight from about 800 Daltons up to about 350 kiloDaltons. Advancementsin solid-phase and solution phase synthesis of amino acid oligomers havemade available techniques to prepare homogeneous polymers or oligomerswith defined sequence and size and these techniques can be adapted tothe present invention.

Polyureas (FIG. 3, IVa), polycarbonates (FIG. 3, IVb) or polyurethanes(FIG. 3, IVc) are carbonic acid derivatives and exhibit propertiessimilar to polyamides (N. Samson et al. J. Appl. Polym. Sci. 65, 2265(1997)). FIG. 3 IVd and IVe depict two different substitution patternswhich can be utilized. Other substitution patterns are equallyeffective.

The polymer design process simply requires a structure in which therepeating sequence of monomers matches the secondary structure adoptedby the backbone. Once the periodicity is observed, monomers substitutedwith polar and nonpolar groups monomers must be prepared and introducedto produce a cationic, amphiphilic secondary. Aromatic polyamides andureas frequently have only a few torsional degrees of freedom per repeat(typically two or four). In this case the secondary structure adopted bythese polymers is most likely planar with polar and nonpolar groupsextended from opposite sides of the backbone. In some cases, the desiredfacial amphiphilicity can be achieved through a simple design principal.

Additional molecular features can be added to the macromolecularbackbone to promote the desired secondary structure and disfavor otherstructures thereby combining elements of both positive and negativedesign. Conformational studies on biofoldamers (proteins and RNA), andearly work with a variety of sequence-specific polymers, have shown thatseveral elements are crucial in order for the polymers to adopt thedesired folded conformation. Key elements include strong electrostaticinteractions (i.e., intramolecular hydrogen bonding) between adjacent ormore distant monomers and rigidification caused by the backbone torsionsor by bulky functional groups. For example, the presence of multiplehydrogen bond donors and acceptors along the macromolecular backbone canlead to extensive intermolecular backbone interactions. Preciseplacement of well designed intramolecular interactions can stabilizedesired secondary structures while at the same time blocking thebackbone hydrogen bond donors which limits intermolecular aggregationproblems. For example, in the polyurea and polyamide a thioether (FIG.3, XIa–c) was positioned between the two aromatic nitrogens to form aninternal hydrogen bond between the sulfur and urea function. This limitsthe torsional angle of the aromatic carbon-urea NH bond by forcing theNH group to be on the same side as the heteroatom, thereby helping todefine the overall sheet-like secondary structure. The secondarystructure for this backbone is predicted to be nearly planar. Similarly,the poly-anthranilate polymer (XIII) is designed based on the finding ofHamuro and Hamilton (Y. Hamuro et al., J. Am. Chem. Soc. 1996119:10587–93) that intramolecular hydrogen-bonding defines the secondarystructure of this class of poly-arylamides.

Magainin and the other naturally occurring antibacterial peptidesexhibit considerable variation in their chain length, hydrophobicity anddistribution of charges. These linear peptides do, however, containpositively charges amino acids and a large hydrophobic moment resultingin a high propensity to adopt α-helical conformations in a hydrophobicenvironment, e.g., a cell surface or a natural or synthetic membrane.(Z. Oren and Y. Shai Biopolymers (Peptide Science), 1998 47, 451–463.)The periodic distribution of hydrophobic and hydrophilic side chains intheir amino acid sequences allows the segregation of the hydrophobic andhydrophilic side chains to opposite faces of the cylinder formed by thehelix. The overall amphiphilicity, not the specific sequence, secondarystructure or chirality, correlates best with anti-microbial activity.Thus it appears that any suitably amphiphilic material (not necessarilyan α-helix or β-sheet) would have anti-microbial properties. Thenecessary condition for forming a facially amphiphilic structure is themolecule should have a repeating pattern of polar and nonpolar sidechains whose periodicity is approximately the same as that of thesecondary structure of interest.

The term “microorganism” as used herein includes bacteria, algae, fungi,yeast, mycoplasmids, parasites and protozoa.

The term “antimicrobial”, “microbiocidal” or “biocidal” as used hereinmeans that the materials inhibit, prevent, or destroy the growth orproliferation of microorganisms. This activity can be eitherbacteriocidal or bacteriostatic. The term “bacteriocidal” as used hereinmeans the killing of microorganisms. The term “bacteriostatic” as usedherein means inhibiting the growth of microorganisms which can bereversible under certain conditions.

The term “polymer” as used herein refers to a macromolecule comprising aplurality of repeating units or monomers. The term includeshomopolymers, which are formed from a single type of monomers andcopolymers that are formed from two or more different monomers. Incopolymers the monomers may be distributed randomly (random copolymer),in alternating fashion (alternating copolymer) or in blocks (blockcopolymer). The polymers of the present invention are eitherhomopolymers or alternating copolymers. The term “polymer” as usedherein is intended to exclude proteins, peptides, polypeptides and otherproteinaceous materials composed exclusively of α or β-amino acids. Theterm “oligomer” as used herein refers to a homogenous polymer with adefined sequence and molecular weight.

The term “polymer backbone” or “backbone” as used herein refers to thatportion of the polymer which is a continuous chain comprising the bondsformed between monomers upon polymerization. The composition of thepolymer backbone can be described in terms of the identity of themonomers from which it is formed without regard to the composition ofbranches, or side chains, off the polymer backbone.

The term “polymer side chain” or “side chain” refers to portions of themonomer which, following polymerization, forms an extension off thepolymer backbone. In homopolymers all the polymer side chains arederived from the same monomer. A copolymer can comprise two or moredistinct side chains from different monomers.

The term “alkyl” as used herein denotes a univalent saturated branchedor straight hydrocarbon chain. Unless otherwise stated such chainscontain from 1 to 18 carbon atoms. Representative of such alkyl groupsare methyl, ethyl, propyl, iso-propyl, sec-butyl, tert-butyl, pentyl,neo-pentyl, iso-pentyl, hexyl, iso-hexyl, heptyl, octyl, nonyl, decyl,tridecyl, tetradecyl, hexadecyl octadecyl, and the like. When qualifiedby “lower” the alkyl group will contain from 1 to 6 carbon atoms. Theterm “cycloalkyl” as used herein denotes a univalent cyclic hydrocarbonchain. Representative groups are cyclopropyl, cyclobutyl, cyclohexyl,cyclopentyl and cyclohexyl.

The phrase “groups with chemically nonequivalent termini” refers tofunctional groups such as esters amides, sulfonamides andN-hydroxyoximes where reversing the orientation of the substituents,e.g. R¹C(═O)OR² vs. R¹O(O═)CR², produces unique chemical entities.

The term “basic heterocycle” as used herein denotes cyclic atomic arraywhich includes a nitrogen atom that has a pKa greater than about 5 andthat is protonated under physiological conditions. Representative ofsuch basic heterocycles are pyridine, quinoline, imidazole, imidazoline,cyclic guanidines, pyrazole, pyrazoline, dihydropyrazo line,pyrrolidine, piperidine, piperazine, 4-alkylpiperazine, and derivativesthereof such as 2-aminopyridine, 4-amninopyridine, 2-aminoimidazoline,4-aminoimidazoline or VII where X¹ is O, N, S or absent and i is 2 to 4.

The term “amphiphilic” as used herein describes a three-dimensionalstructure having discrete hydrophobic and hydrophilic regions. Anamphiphilic polymer requires the presence of both hydrophobic andhydrophilic elements along the polymer backbone. The presence ofhydrophobic and hydrophilic groups is a necessary, but not sufficient,condition to produce an amphiphilic molecule or polymer. Polymersfrequently adopt a random or disordered conformation in which the sidechains are located randomly in space and there are no distinctivehydrophobic and hydrophilic regions.

The term “facially amphiphilic” or “facial amphiphilicity” as usedherein describes polymers with polar (hydrophilic) and nonpolar(hydrophobic) side chains that adopt conformation(s) leading tosegregation of polar and nonpolar side chains to opposite faces orseparate regions of the structure. This structure can comprise any ofthe energetically accessible low-energy conformations for a givenpolymer backbone. Additionally random or block copolymers may adoptrandom backbone conformations that do not lead to distinct hydrophilicand hydrophobic regions or which do not segregate along different facesof the polymer. These copolymers are not facially amphiphilic as definedherein.

The term “naturally occurring amino acids” means the L-isomers of thenaturally occurring amino acids. The naturally occurring amino acids areglycine, alanine, valine, leucine, isoleucine, serine, methionine,threonine, phenylalanine, tyrosine, tryptophan, cysteine, proline,histidine, aspartic acid, asparagine, glutamic acid, glutamine,carboxyglutamic acid, arginine, omithine and lysine. Unless specificallyindicated, all amino acids referred to in this application are in theL-form.

The term “side chain of a naturally occurring amino acid” as used hereinrefers to the substituent on the a-carbon of a amino acid. The tern“polar side chain of a naturally occurring amino acid” refers to theside chain of a positively charged, negatively charged or hydrophilicamino acid. The term “nonpolar side chain of a naturally occurring aminoacid” refers to the side chain of a hydrophobic amino acid.

The term “positively charged amino acid” or “cationic amino acid” asused herein includes any naturally occurring or unnatural amino acidhaving a positively charged side chain under normal physiologicalconditions. Examples of positively charged naturally occurring aminoacids are arginine, lysine and histidine.

The term “hydrophilic amino acid” means any amino acid having anuncharged, polar side chain that is relatively soluble in water.Examples of naturally occurring hydrophilic amino acids are serine,threonine, tyrosine, asparagine, glutamine, and cysteine.

The term “hydrophobic amino acid” means any amino acid having anuncharged, nonpolar side chain that is relatively insoluble in water.Examples of naturally occurring hydrophobic amino acids are alanine,leucine, isoleucine, valine, proline, phenylalanine, tryptophan andmethionine.

One embodiment of the present invention is a polymeric compound offormula I

wherein:

-   -   x is NR³, O, or S, y is C═O, C═S, O═S═O, or —C(═O)C(═O)— and R³        is hydrogen, methyl or ethyl;    -   either both A and B are independently optionally substituted o-,        m-, p-phenylene,        -   or optionally substituted heteroarylene wherein (i) A and B            are both substituted with a polar (P) group and a nonpolar            (NP) group, (ii) one of A and B is substituted with a            polar (P) group and a nonpolar (NP) group and the other of A            and B is substituted with neither a polar nor a nonpolar            group, or (iii) one of A or B is substituted with a            polar (P) group and the other of A or B is substituted with            a nonpolar (NP) group; or,        -   one of A and B is o-, m-, p-phenylene or heteroarylene—the            other of A and B is a C₃ to C₈ cycloalkyl or (CH₂)_(q) where            q is 1 to 7 wherein (i) one of A or B is optionally            substituted by one or more polar (P) group(s) and the other            of A or B is optionally substituted with one or more            nonpolar (NP) group(s), or (ii) A is substituted with a            polar (P) group and a nonpolar (NP) group and B is a C₃ to            C₈ cycloalkyl or (CH₂)_(q) where q is 1 to 7 and B is            optionally independently substituted with one or more            polar (P) or nonpolar (NP) group;    -   R¹ is (i) -y-C and R² is OH or NH₂ wherein C is selected from a        group consisting of C₁–C₆ allcyl, vinyl, 2-propenyl,        H-x-(CH₂)_(p)—, (C₁–C₆-alkoxy)C(═O)(CH₂)_(p)—, C₁–C₆ alkoxy,        benzyloxy, t-butoxy, pyridine and phenyl said pyridine or phenyl        optionally substituted with 1 or 2 substituents independently        selected from a group consisting of halo, nitro, cyano, C₁–C₆        alkoxy, C₁–C₆ alkoxycarbonyl, and benzyloxycarbonyl; or, (ii) is        H and R² is -x-(CH₂)_(p)—W wherein x is as defined above and p        is as defined below and W is N-maleimide or V as defined below,        or (iii) R₁ and R₂ together are a single bond;    -   NP is a nonpolar group an independently selected from R⁴ or        —U—(CH₂)_(p)—R⁴ wherein R⁴ is selected from a group consisting        of hydrogen, C₁–C₁₀ alkyl, C₃–C₁₈ branched alkyl, C₃–C₈        cycloalkyl, monocyclic or polycyclic phenyl optionally        substituted with one or more C₁–C₄ alkyl, C₁–C₄ alkoxy or halo        groups and monocyclic or polycyclic heteroaryl optionally        substituted with one or more C₁–C₄ alkyl, C₁–C₄ alkoxy, or halo        groups and U and p are as defined below;    -   P is a polar group selected from a group consisting of IIIa,        hydroxyethoxymethyl, methoxyethoxymethyl and polyoxyethylene        —U—(CH₂)_(p)—V  (IIIa)    -    wherein,        -   U is absent or selected from a group consisting of O, S,            S(═O), S(═O)₂, NH, —C(═O)O—, —C(═O)NH—, —C(═O)S—, —C(═S)NH—,            —S(═O)₂NH—, and C(═NO—) wherein groups with two chemically            nonequivalent termini can adopt both possible orientations;        -   V is selected from a group consisting of amino, hydroxyl,            thio, C₁–C₆ alkylamino, C₁–C₆ dialkylamino, NH(CH₂)_(p)NH₂,            N(CH₂CH₂NH₂)₂, amidine, guanidine, semicarbazone, C₁–C₆            alkoxycarbonyl, basic heterocycle, and phenyl optionally            substituted with an amino, C₁–C₆ alkylamino, C₁–C₆            dialkylamino and lower acylamnino optionally substituted            with one or more amino, lower alkylamino or lower            dialkylamino;        -   and the alkylene chain is optionally substituted with an            amino or hydroxyl group or unsaturated;    -   p is independently 0 to 8;    -   m is 2 to at least about 500.

Another embodiment of polymer compound of formula VII:

wherein

-   -   one of R⁹ or R¹⁰ and R¹¹ is a polar (P) group and the other of        R⁹ or R¹⁰ and R¹¹ is a nonpolar (NP) group;    -   P is a polar group selected from a group consisting of IIIb,        hydroxyethoxymethyl, methoxyethoxymethyl or polyoxyethylene        —(CH₂)_(p)—V  (IIIb)    -    wherein:        -   V is selected from a group consisting of amino, hydroxyl,            C₁–C₆ allcylamino, C₁–C₆ dialkylamino, NH(CH₂)_(p)NH₂,            N(CH₂CH₂NH₂)₂, amidine, guanidine, semicarbazone, imidazole,            piperidine, piperazine, 4-alkylpiperazine and phenyl            optionally substituted with an amino, C₁–C₆ alkylamino,            C₁–C₆ dialkylamino and lower acylamino optionally            substituted with one or more amino, lower alkylamino or            lower dialkylamino; and,        -   the alkylene chain is optionally substituted with an amino            or hydroxyl group;    -   p is independently 0 to 8; and,    -   m is 2 to at least about 30.

Still another embodiment of the present invention is a polyrnericcompound of formula IX

wherein:

-   -   -   one of R⁹ or R¹¹ is either a polar (P) group or a nonpolar            (NP) group and the other of R⁹ or R¹¹ is the other of a            polar (P) group or a nonpolar (NP) group;

    -   NP is —(CH₂)_(p)—R⁴ wherein R⁴ is selected from a group        consisting of hydrogen, C₁–C₄ alkyl, C₃–C₁₂ branched alkyl,        C₃–C₈ cycloalkyl, phenyl optionally substituted with one or more        C₁–C₄ alkyl groups C₁–C₄ alkoxy or halo groups and heteroaryl        optionally substituted with one or more C₁–C₄ alkyl group, C₁–C₄        alkoxy or halo groups and p is as defined below;

    -   P is a polar group selected from a group consisting of IIIb,        hydroxyethoxymethyl, methoxyethoxymethyl or polyoxyethylene        —(CH₂)_(p)—V  (IIIb)

    -    wherein:        -   V is selected from a group consisting of amino, hydroxyl,            C₁–C₆ alkylamino, C₁–C₆ dialkylamino, NH(CH₂)_(p)NH₂,            N(CH₂CH₂NH₂)₂, amidine, guanidine, semicarbazone, imidazole,            piperidine, piperazine, 4-alkylpiperazine and phenyl            optionally substituted with an amino, C₁–C₆ alkylamino,            C₁–C₆ dialkylamino and lower acylamino optionally            substituted with one or more amino, lower alkylamino or            lower dialkylamino; and,        -   the alkylene chain is optionally substituted with an amino            or hydroxyl group.

    -   p is independently 0 to 8.

An embodiment of the present invention is a polymeric compound offormula IX wherein R⁹ is a polar side chain of a natural amino acids andR¹¹ is selected from a group consisting of methyl, ethyl, n-propyl,iso-propyl, n-butyl iso-butyl, sec-butyl, tert-butyl, n-pentyl,iso-pentyl, sec-pentyl, and benzyl.

Another embodiment of the present invention is polymeric compound offormula IX wherein R⁹ is a nonpolar side chain of a natural amino acidsand R¹¹ is a polar group selected from a group consisting of IIIb,hydroxyethoxymethyl, methoxyethoxymethyl or polyoxyethylene—(CH₂)_(p)—V  (IIIb)

-   -    wherein:        -   V is selected from a group consisting of amino, hydroxyl,            C₁–C₆ alkylamino, C₁–C₆ dialkylamino, NH(CH₂)_(p)NH₂,            N(CH₂CH₂NH₂)₂, amidine, guanidine, semicarbazone, imidazole,            piperidine, piperazine, 4-alkylpiperazine and phenyl            optionally substituted with an amino, C₁–C₆ alkylamino,            C₁–C₆ dialkylamino and lower acylamino optionally            substituted with one or more amino, lower alkylamino or            lower dialkylamino; and,    -   p is independently 0 to 8.

Still another embodiment of the present invention is a polymericcompound of formula I wherein:

-   -   x is NH and y is C═O or C═S;    -   A and B are independently optionally substituted o-, m-, or        p-phenylene, 2,5-thiophenylene or 2,5-pyrrolene;    -   NP is a nonpolar group independently selected from R⁴ or        —U—(CH₂)_(p)—R⁴ wherein R⁴ is selected from a group consisting        of hydrogen, C₁–C₄ alkyl, C₃–C₁₂ branched alkyl, C₃–C ₈        cycloalkyl, phenyl optionally substituted with one or more C₁–C₄        alkyl groups C₁–C₄ alkoxy or halo groups and heteroaryl        optionally substituted with one or more C₁–C₄ alkyl group, C₁–C₄        alkoxy or halo groups and U and p are as defined below;    -   P is a polar group selected from a group consisting of IIIa,        hydroxyethoxymethyl, methoxyethoxymethyl or polyoxyethylene        —U—(CH₂)_(p)—V  (IIIa)    -    wherein:        -   U is absent, O, S, SO, SO₂, or NH;        -   V is selected from a group consisting of amino, hydroxyl,            C₁–C₆ alkylamino, C₁–C₆ dialkylamino, NH(CH₂)_(p)NH₂,            N(CH₂CH₂NH₂)₂, amidine, guanidine, semicarbazone, imidazole,            piperidine, piperazine, 4-alkylpiperazine and phenyl            optionally substituted with an amino, C₁–C₆ alkylamino,            C₁–C₆ dialkylamino and lower acylamino optionally            substituted with one or more amino, lower alkylamino or            lower dialkylamino; and,        -   the alkylene chain is optionally substituted with an amino            or hydroxyl group;    -   p is independently 0 to 8; and,    -   m is 2 to at least about 500.

An embodiment of the present invention is a polymeric compound offormula I wherein:

-   -   x is NR³, R³ is hydrogen, and y is C═O or C═S;    -   A and B are independently optionally substituted o-, m-, or        p-phenylene;    -   NP is a nonpolar group independently selected from R⁴ or        —U—(CH₂)_(p)—R⁴ wherein R⁴ is selected from a group consisting        of hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl,        iso-butyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, and        sec-pentyl and U and p are as defined below;    -   P is a polar group U—(CH₂)_(p)—V wherein U is absent or selected        from a group consisting of O and S, and V is selected from a        group consisting of amino, lower alkyl amino, lower        dialkylamino, imidazole, guanidine, NH(CH₂)_(p)NH₂,        N(CH₂CH₂NH₂)₂, pyridine, piperidine, piperazine,        4-alkylpiperazine; and    -   p is independently 0 to 8;    -   m is 2 to at least about 500.

Another embodiment of the present invention is a polymeric compound offormula I wherein:

-   -   x is NR³, y is CO, and R³ is hydrogen;    -   A and B are m- or p-phenylene wherein (i) A is substituted at        the 2-position with a polar (P) group and B is substituted at        the 5-position with a nonpolar (NP) group, (ii) A is substituted        at the 2-position with a polar (P) group and at the 5-position        with a nonpolar (NP) group and B is substituted at the        2-position with a nonpolar (NP) group and at the 5-position with        a polar (P) group or, (iii) A is substituted at the 2-position        with one of a polar (P) or nonpolar (NP) group and B is        substituted at the 2-position with the other of a nonpolar (NP)        or a polar (P) group;    -   NP is a nonpolar group independently selected from R⁴ or —U—R⁴        wherein R⁴ is selected from a group consisting of methyl, ethyl,        n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,        n-pentyl, iso-pentyl, and sec-pentyl and U and p are as defined        below;    -   p is independently 0 to 8; and,    -   m is 2 to at least about 500.

Still another embodiment of the present invention is a polymericcompound of formula XII

wherein:

-   -   NP is a nonpolar group independently selected from a group        consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl,        iso-butyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, and        sec-pentyl and U and p are as defined below;    -   P is a polar group U—(CH₂)_(p)—V wherein U is selected from a        group consisting of O, S, or no atom and V is selected from a        group consisting of amino, lower alkyl amino, lower        dialkylamino, imidazole, guanidine, NH(CH₂)_(p)NH₂, and        N(CH₂CH₂NH₂)₂, piperidine, piperazine, 4-alkylpiperazine; and,    -   p is independently 0 to 8;    -   m is 2 to at least about 30.

Yet another embodiment of the present invention is a polymer accordingto claim 8 comprising a compound of formula XIV,

wherein:

-   -   NP is a nonpolar group independently selected from R⁴ or —U—R⁴        wherein R⁴ is selected from a group consisting of methyl, ethyl,        n-propyl, iso-propyl, 12-butyl, iso-butyl, sec-butyl,        tert-butyl, n-pentyl, iso-pentyl, and sec-pentyl and U and p are        as defined below;    -   P is a polar group U—(CH₂)_(p)—V wherein U is selected from a        group consisting of O, S, or no atom and V is selected from a        group consisting of amino, lower alkyl amino, lower        dialkylamino, imidazole, guanidine, NH(CH₂)_(p)NH₂, and        N(CH₂CH₂NH₂)₂, piperidine, piperazine, 4-alkylpiperazine; and,    -   p is independently 0 to 8;    -   m is 2 to at least about 30.

Yet another embodiment of the present invention is a polymeric compoundof formula I wherein:

-   -   x is NR³, y is CO, and R³ is hydrogen;    -   A and B are o-phenylene wherein A is substituted at the        5-position with a polar (P) group and B is substituted at the        5-position with a nonpolar (NP) group;    -   NP is a nonpolar group independently selected from R⁴ or —U—R⁴        wherein R⁴ is selected from a group consisting of methyl, ethyl,        n-propyl, iso-propyl, iso-butyl, n-butyl, sec-butyl, tert-butyl,        n-pentyl, iso-pentyl, and sec-pentyl and U and p are as defined        below;    -   P is a polar group U—(CH₂)_(p)—V wherein U is selected from a        group consisting of O, S, or no atom and V is selected from a        group consisting of amino, lower alkyl amino, lower        dialkylamino, imidazole, guanidine, NH(CH₂)_(p)NH₂, and        N(CH₂CH₂NH₂)₂, pyridine, piperidine, piperazine,        4-alkylpiperazine;    -   p is independently 0 to 8; and,    -   m is 2 to at least about 500.

Another embodiment of the present invention is a polymeric compound offormula XIII:

wherein:

-   -   NP is a nonpolar group independently selected from a the group        consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl,        iso-butyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, and        sec-pentyl and U and p are as defined below;    -   P is a polar group (CH₂)_(p)—V wherein V is selected from a        group consisting of amino, lower alkyl amino, lower        dialkylamino, guanidine, piperazine, 4-alkylpiperazine;

-   p is independently 0 to 8;

-   m is 2 to at least about 30.

An embodiment of the present invention is a polymeric compound offormula XV:

wherein

-   -   either R¹² and R¹⁴ are independently polar (P) groups and R¹³        and R¹⁵ are independently nonpolar (NP) groups substituted at        one of the remaining unsubstituted carbon atoms, or R¹² and R¹⁴        are independently nonpolar (NP) groups and R¹³ and R¹⁵ are        independently polar (P) groups    -   NP is a nonpolar group independently selected from R⁴ or —U—R⁴        wherein R⁴ is selected from a the group consisting of methyl,        ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl,        tert-butyl, n-pentyl, iso-pentyl, and sec-pentyl and U is        defined below;    -   P is a polar group U—(CH₂)_(p)—V wherein U is selected from a        group consisting of O or S and V is selected from a group        consisting of amino, lower alkyl amino, lower dialkylamino,        guanidine, pyridine, piperazine, 4-alkylpiperazine;    -   p is independently 0 to 8;    -   m is 2 to at least about 30.

An embodiment of the present invention is a polymeric compound offormula II wherein:

-   -   x and y can be (i) taken independently wherein x is NR³, O, S,        (CR⁷R⁸)NR³, (CR⁷R⁸), or (CR⁷R⁸)S, y is C═O, C═S, O═S═O,        —C(═O)C(═O)—, (CR⁵R⁶)C═O or (CR⁵R⁶)C═S, and R³ is hydrogen,        methyl or ethyl; or, (ii) taken together to be pyromellitic        diimide; and R⁵ and R⁶ together are (CH₂)₂NR¹²(CH₂)₂ and R¹² is        selected from a group consisting of hydrogen —C(═N)CH₃ or        C(═NH)—NH₂; and R⁷ and R⁸ together are (CH₂)_(p) wherein p is as        defined below;    -   both A and B are independently optionally substituted o-, m-,        p-phenylene, or optionally substituted heteroarylene wherein (i)        A and B are both substituted with a polar (P) group and a        nonpolar (NP) group, (ii) one of A and B is substituted with a        polar (P) group and a nonpolar (NP) group and the other of A and        B is substituted with neither a polar nor a nonpolar group,        or (iii) one of A or B is substituted with a polar (P) group and        the other of A or B is substituted with a nonpolar (NP) group;    -   R¹ is (i) —B-y-R² and R² is -x-(CH₂)_(p)—W wherein x is as        defined above and W is hydrogen, phenyl optionally substituted        with up to three substituents selected from a group consisting        of halogen, C₁–C₄ alkyl, C₁–C₄ alkoxy, and carboxyl,        N-maleimide, or V as defined below, and p is an defined below;        or, (ii) R¹ and R² together are a single bond    -   NP is a nonpolar group an independently selected from R⁴ or        —U—(CH₂)_(p)—R⁴ wherein R⁴ is selected from a group consisting        of hydrogen, C₁–C₁₀ alkyl, C₃–C ₁₈ branched alkyl, C₃–C ₈        cycloalkyl, monocyclic or polycyclic phenyl optionally        substituted with one or more C₁–C₄ alkyl, C₁–C₄ alkoxy or halo        groups and monocyclic or polycyclic heteroaryl optionally        substituted with one or more C₁–C₄ alkyl, C₁–C₄ alkoxy, or halo        groups and U and p are as defined below;    -   P is a polar group selected from a group consisting of IIIa,        hydroxyethoxymethyl, methoxyethoxymethyl and polyoxyethylene        —U—(CH₂)_(p)—V  (IIIa)    -    wherein,        -   U is absent or selected from a group consisting of O, S,            S(═O), S(═O)₂, NH, —C(═O)O—, —C(═O)NH—, —C(═O)S—, —C(═S)NH—,            —S(═O)₂NH—, and C(═NO—) wherein groups with two chemically            nonequivalent termini can adopt both possible orientations;        -   V is selected from a group consisting of amino, hydroxyl,            thio, C₁–C₆ alkylamino, C₁–C₆ dialkylamino, NH(CH₂)_(p)NH₂,            N(CH₂CH₂NH₂)₂, amidine, guanidine, semicarbazone, C₁–C₆            alkoxycarbonyl, basic heterocycle, and phenyl optionally            substituted with an amino, C₁–C₆ alkylamino, C₁–C₆            dialkylamino and lower acylamino optionally substituted with            one or more amino, lower alkylamino or lower dialkylamino;        -   and the alkylene chain is optionally substituted with an            amino or hydroxyl group or unsaturated;    -   p is independently 0 to 8;    -   m is 2 to at least about 500.

Another embodiment of the present invention is a polymeric compound offormula II wherein:

-   -   x=NH and y=CO;    -   A and B are m- or p-phenylene wherein (i) A is substituted at        the 2-position with a polar (P) group and B is substituted at        the 5-position with a nonpolar (NP) group, or (ii) A is        substituted at the 2-position with a polar (P) group and at the        5-position with a nonpolar (NP) group and B is either        substituted at the 2-position with a nonpolar (NP) group and at        the 5-position with a polar (P) group or B is unsubstituted;    -   NP is a nonpolar group independently selected from R⁴ or        —U—(CH₂)_(p)—R⁴ wherein R⁴ is selected from a group consisting        of methyl, ethyl, n-propyl, iso-propyl, iso-butyl, sec-butyl,        tert-butyl, iso-pentyl, and sec-pentyl and U and p are as        defined below;    -   P is a polar group U—(CH₂)_(p)—V wherein U is absent or selected        from a group consisting of O and S, and V is selected from a        group consisting of amino, lower alkyl amino, lower        dialkylamino, imidazole, guanidine, NH(CH₂)_(p)NH₂,        N(CH₂CH₂NH₂)₂, piperidine, 4-alkylpiperazine and;    -   p is independently 0 to 8;    -   m is 2 to at least about 500.

Yet another embodiment of the present invention is a polymeric compoundof formula II where A is an optionally substituted 1,3-diaminobenzeneand B is an optionally substituted iso-phthalic acid.

Still another embodiment of the present invention is a polymericcompound of formula XI

wherein:

-   -   R⁴ is selected from a group consisting of methyl, ethyl,        n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,        ii-pentyl, iso-pentyl, and sec-pentyl;    -   U is O or S;    -   V is amino, lower alkyl amino, lower dialkylamino, guanidine;    -   p is independently 0–8;    -   m is 2 to at least about 30.

Another embodiment of the present invention is a polymeric compound offormula XVI

wherein:

-   -   either R¹² and R¹⁴ are independently polar (P) groups and R¹³        and R¹⁵ are independently nonpolar (NP) groups substituted at        one of the remaining unsubstituted carbon atoms, or R¹² and R¹⁴        are independently nonpolar (NP) groups and R¹³ and R¹⁵ are        independently polar (P) groups    -   NP is a nonpolar group independently selected from R⁴ or —U—R⁴        where R⁴ is selected from a group consisting of methyl, ethyl,        n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,        n-pentyl, iso-pentyl, and sec-pentyl, and U is as defined below;    -   P is a polar group U—(CH₂)_(p)—V wherein U is absent or selected        from a group consisting of O and S, and V is selected from a        group consisting of amino, lower alkyl amino, lower        dialkylamino, imidazole, guanidine, NH(CH₂)_(p)NH₂,        N(CH₂CH₂NH₂)₂, piperidine, and 4-alkylpiperazine;    -   U is O or S;    -   V is amino, lower alkyl amino, lower dialkylamino, guanidine;    -   p is independently 0 to 8; and    -   m is 2 to at least about 30.

Still another embodiment of the present invention is a polymericcompound of formula XX

wherein j is independently 0 or 1, R⁵ and R⁶ together are (CH₂)₂NH(CH₂)₂and R⁷ and R⁸ together are (CH₂)_(p) wherein p is 4 to 6.

Yet another embodiment of the present invention is a polymeric compoundof formula IV

wherein:

-   -   x is NR³ or NHNH and y is NR³, NHNH, S or O, and R³ is hydrogen,        methyl or ethyl;    -   z is C═O, —(C═O)C(═O)—, C═S or O═S═O;    -   A and B are independently optionally substituted o-, m-,        p-phenylene or optionally substituted heteroarylene wherein (i)        A and B are both substituted with a polar (P) group and a        nonpolar (NP) group (NP), (ii) one of A and B is substituted        with a polar (P) group and a nonpolar (NP) group and the other        of A and B is substituted with neither a polar nor a nonpolar        group, or (iii) one of A or B is substituted with one or two        polar (P) group(s) and the other of A or B is substituted with        one or two nonpolar (NP) group(s), or, or (iv) A is substituted        at the 2-position with a polar (P) group and at the 5-position        with a nonpolar (NP) group and B is unsubstituted;    -   R¹ is (i) —B-y-R² and R² is -x-(CH₂)_(p)—W wherein x is as        defined above and W is hydrogen, pyridine and phenyl said        pyridine or phenyl optionally substituted with 1 or 2        substituents independently selected from a group consisting of        halo, nitro, cyano, C₁–C₆ alkoxy, C₁–C ₆ alkoxycarbonyl, and        benzyloxycarbonyl; R¹ is H and R² is -x-(CH₂)_(p)—V or (ii) R₁        and R₂ together are a single bond;    -   NP is a nonpolar group independently selected from R⁴ or        —U—(CH₂)_(p)—R⁴ wherein R⁴ is selected from a group consisting        of C₁–C₁₈ alkyl, C₃–C₁₈ branched alkyl, C₃–C₈ cycloalkyl,        monocyclic or polycyclic phenyl optionally substituted with one        or more C₁–C₄ alkyl or halo groups, and monocyclic or polycyclic        heteroaryl optionally substituted with one or more C₁–C₄ alkyl        or halo groups and U and p are as defined below;    -   P is a polar group selected from a group consisting of IIIa,        hydroxyethoxymethyl, methoxyethoxymethyl and polyoxyethylene        —U—(CH₂)_(p)—V  (IIIa)    -    wherein;        -   U is absent or selected from a group consisting of O, S,            S(═O), S(═O)₂, NH, —C(═O)O—, —C(═O)NH—, —C(═O)S—, —C(═S)NH—,            —S(═O)₂NH—, and C(═NO—) wherein groups with two chemically            nonequivalent termini can adopt both possible orientations;        -   V is selected from a group consisting of amino, hydroxyl,            C₁–C₆ alkylamino, C₁–C₆ dialkylamino, NH(CH₂)_(p)NH₂,            N(CH₂CH₂NH₂)₂, amidine, guanidine, semicarbazone, basic            heterocycle, and phenyl optionally substituted with an            amino, C₁–C₆ alkylamino, C₁–C₆ dialkylamino and lower            acylamino optionally substituted with one or more amino,            lower alkylamino or lower dialkylamino;        -   and the alkylene chain is optionally substituted with an            amino or hydroxyl group or optionally unsaturated;    -   p is independently 0 to 8;    -   m is 2 to at least about 500.

Yet another embodiment of the present invention is a polymeric compoundof formula IV wherein:

-   -   x and y are NR³, z is C═O or C═S, and R³ is hydrogen;    -   A and B are independently optionally substituted o-, m-, or        p-phenylene;    -   NP is a nonpolar group independently selected from R⁴ or        —U—(CH₂)_(p)—R⁴ wherein R⁴ is selected from a group consisting        of hydrogen, C₁–C₄ alkyl, C₃–C₁₂ branched alkyl, C₃–C₈        cycloalkyl, phenyl optionally substituted with one or more C₁–C₄        alkyl groups and heteroaryl optionally substituted with one or        more C₁–C₄ alkyl groups and U and p are as defined below;    -   P is a polar group selected from consisting of IIIa,        hydroxyethoxymethyl, methoxyethoxymethyl or polyoxyethylene        —U—(CH₂)_(p)—V  (IIIa)    -    wherein        -   U is O, S, S(═O), S(═O)₂, NH, or absent;        -   V is selected from a group consisting of amino, hydroxyl,            C₁–C₆ alkylamino, C₁–C₆ dialkylamino, NH(CH₂)_(p)NH₂,            N(CH₂CH₂NH₂)₂, amidine, guanidine, semicarbazone, and            imidazole, piperidine, piperazine, 4-alkylpiperazine and            phenyl optionally substituted with an amino, C₁–C₆            alkylamino, C₁–C₆ dialkylamino and lower acylamino            optionally substituted with one or more amino, lower            alkylamino or lower dialkcylamino;        -   and the alkylene chain is optionally substituted with an            amino or hydroxyl group;    -   p is independently 0 to 8; and,    -   m is 2 to at least about 500.

An embodiment of the present invention is a polymeric compound offormula IV wherein:

-   -   x and y are NH, z is C═O;    -   A and B are m- or p-phenylene and either (i) A is substituted at        the 2-position with a polar (P) group and B is substituted at        the 5-position with a nonpolar (NP) group, or (ii) A is        substituted at the 5-position with a polar (P) group and B is        substituted at the 2-position with a nonpolar (NP) group,        or (iii) A and B are both substituted at the 2-position with a        polar (P) group and at the 5-position with a nonpolar (NP)        group, or (iv) A is substituted at the 2-position with a        polar (P) group and at the 5-position with a nonpolar (NP) group        and B is unsubstituted;    -   NP is a nonpolar group independently selected from R⁴ or        —U—(CH₂)_(p)—R⁴ wherein R⁴ is selected from a group consisting        of hydrogen, methyl, ethyl, n-propyl, iso-propyl, iso-butyl,        sec-butyl, tert-butyl, iso-pentyl, and sec-pentyl and U and p        are as defined below;    -   P is a polar group U—(CH₂)_(p)—V wherein U is absent or selected        from a group consisting of O, S and V is selected from a group        consisting of amino, lower alkyl amino, lower dialkylamino,        imidazole, guanidine, NH(CH₂)_(p)NH₂, and N(CH₂CH₂NH₂)₂,        piperidine, piperazine, 4-alkylpiperazine;    -   p is independently 0 to 8; and,    -   m is 2 to at least about 500.

Another embodiment of the present invention is a polymeric compound offormula XIV

-   -   R⁴ is selected from a group consisting of methyl, ethyl,        n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,        n-pentyl, iso-pentyl, and sec-pentyl and U and p are as defined        below;    -   U is absent, O or S and V is selected from a group consisting of        amino, lower alkyl amino, lower dialkylamino, imidazole,        guanidine, NH(CH₂)_(p)NH₂, and N(CH₂CH₂NH₂)₂, piperidine,        piperazine, 4-alkylpiperazine; and,    -   p is 0 to 8;    -   m is 2 to at least about 30.

Still another embodiment of the present invention is a polymericcompound of formula XVII

wherein:

-   -   either R¹² and R¹⁴ are independently polar (P) groups and R¹³        and R¹⁵ are independently nonpolar (NP) groups substituted at        one of the remaining unsubstituted carbon atoms, or R¹² and R¹⁴        are independently nonpolar (NP) groups and R¹³ and R¹⁵ are        independently polar (P) groups    -   NP is a nonpolar group independently selected from R⁴ or —U—R⁴        wherein R⁴ is selected from a the group consisting of methyl,        ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl,        tert-butyl, n-pentyl, iso-pentyl, and sec-pentyl and U and p are        as defined below;    -   P is a polar group U—(CH₂)_(p)—V wherein U is selected from a        group consisting of O or S and V is selected from a group        consisting of amino, lower alkyl amino, lower dialkylamino,        guanidine, pyridine, piperazine, 4-alkylpiperazine;    -   p is independently 0 to 8; and,    -   m is 2 to at least about 30.

Another embodiment of the present invention is a polymeric compound offormula XVIII

wherein:

-   -   NP is a nonpolar group independently selected from R⁴ or        —(CH₂)_(p)—R⁴ wherein R⁴ is selected from a group consisting of        hydrogen methyl, ethyl, n-propyl, iso-propyl, n-butyl,        iso-butyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, and        sec-pentyl and p is as defined below;    -   P is a polar group (CH₂)_(p)—V wherein V is selected from a        group consisting of amino, lower alkyl amino, lower        dialkylamino, imidazole, guanidine, NH(CH₂)_(p)NH₂, and        N(CH₂CH₂NH₂)₂, piperidine, piperazine, 4-alkylpiperazine;    -   p is independently 0 to 8; and,    -   m is 2 to at least about 30.

Polyamides and polyesters that are useful for the present invention canbe prepared by typical condensation polymerization and additionpolymerization processes. [G. Odian, Principles of Polymerization, JohnWiley & Sons, Third Edition (1991), M. Steven, Polymer Chemistry, OxfordUniversity Press, (1999)] Most commonly the polyamides are prepared by(a) thermal dehydration of amine salts of carboxylic acids, (b) reactionof acid chlorides with amines and (c) aminolysis of esters. Methods (a)and (c) are of limited use in polymerizations of aniline derivativeswhich are generally prepared utilizing acid chlorides. The skilledchemist, however, will recognize that there are many alternative activeacylating agents, for example phosphoryl anhydrides, active esters orazides, which may replace an acid chloride and which, depending of theparticular polymer being prepared, may be superior to an acid chloride.The acid chloride route is probably the most versatile and has been usedextensively for the synthesis of aromatic polyamides

Homopolymers derived from substituted aminobenzoic acid derivatives(FIG. 1) can also prepared in a stepwise fashion. A stepwise processcomprises coupling an N-protected amino acid to an amine (or hydroxygroup) and subsequently removing the amine-protecting group andrepeating the process. These techniques have been highly refined forsynthesis of specific peptides, allow for the synthesis of specificsequences, and both solid-phase and solution techniques for peptidesynthesis are directly applicable to the present invention. Analternative embodiment of the present invention is the correspondingpolysulfonamides that can be prepared in analogous fashion bysubstituting sulfonyl chlorides for carboxylic acid chlorides.

The most common method for the preparation of polyureas is the reactionof diamines with diisocyanates. (Yamaguchi, I. et al. Polym. Bull. 200044, 247) This exothermic reaction can be carried out by solutiontechniques or by interfacial techniques. One skilled in organic andpolymer chemistry will appreciate that the diisocyanate can be replacedwith a variety of other bis-acylating agents e.g., phosgene or N,N′-(diimidazolyl)carbonyl, with similar results. Polyurethanes areprepared by comparable techniques using a diisocyanate and a dialcoholor by reaction of a diamine with a bis-chloroformate.

The syntheses of appropriately substituted monomers are straightforward.Numerous pathways are available to incorporate of polar and nonpolarside chains. Phenolic groups on the monomer can be alkylated. Alkylationof the commercially available phenol will be accomplished with standardWilliamson ether synthesis for the non-polar side chain with ethylbromide as the alkylating agent. Polar sidechains can be introduced withbifunctional alkylating agents such as BOC-NH(CH₂)₂Br. Alternatively thephenol group can be alkylated to install the desired polar side chainfunction by employing Mitsonobu reaction with BOC-NH(CH₂)₂—OH, triphenylphosphine, and diethyl acetylenedicarboxylate, Standard conditions forreduction of the nitro groups and hydrolysis of the ester afford theamino acid. With the aniline and benzoic acid in hand coupling can beeffected under a variety of conditions. Alternatively the hydroxy groupof the (di)nitrophenol can be converted to a leaving group andfunctionality introduced under nucleophilic aromatic substitutionconditions (FIG. 8). Other potential scaffolds that can be prepare withsimilar sequences are methyl 2-nitro-4-hydroxybenzoate (FIG. 9) andmethyl 2-hydroxy-4-nitrobenzoate.

Antimicrobial testing is carried out using the micro-broth dilutiontechnique with E. coli. Other organisms screened include ampicillin &streptomycin-resistant E. coli D31, B. subtilis, vancomycin-resistantEnterococcus faecium A436, and methicillin-resistant S. aureus 5332. Anypeptide that is found to be active will be purified to homogeneity, andretested to obtain an accurate IC₅₀. Secondary screens includeKlebsiella pneumoniae Kp1, and Salmonella typhimunium S5, andPseudomonus aeruginosa 10. Traditionally, the micro-broth dilutiontechnique only evaluates a single data point between 18–24 hours;however, the measurements can be extended to 24 hr to monitor cellgrowth through the entire growth phase. These experiments are performedin LB medium (which is a rich medium typically used to grow cells forprotein expression) and represent a critical initial screen foractivity. Since salt concentrations, proteins, and other solutes canaffect the activities of antibiotics, materials that showed no activityin rich medium were retested in minimal medium (M9) to determine if richmedium was limiting activity. No relationship between the media and theactivity was observed which is consistent with the mode of action isbelieved to be through general membrane disruption.

To determine the toxicity to mammalian, as well to bacterial, cells thebiocidal activity is evaluated using both cultured cells and freshlyobtained human blood cells. Increasing concentration of polymer will beadded to both confluent and non-confluent cultures of human umbilicalendothelial cells (HUVEC, Cambrex). Cell number, monolayer integrity,and cell viability (measured as trypan blue exclusion) will be evaluatedas a function of time in culture.

While the synthesis of a variety of polymer backbones is wellunderstood, computer-aided computational techniques can provide valuableinsight and guidance in the selection of potential antimicrobialpolymers. The goal of these computations is to identify potential lowenergy conformations which have a geometrical repeat that matches aconvenient sequence repeat of less than 6 monomer units. For example inα-amino acid oligomers, the geometrical repeat of the β-sheet is 2.0residues. Once these repeating scaffolds are identified and thefrequency of the repeat is calculated, polar and nonpolar substituentscan be incorporated into the monomers to confer amphiphilic propertiesinto the molecule.

High level ab initio calculations are one technique which will identifyaccessible low energy conformations. Unfortunately, these techniques,while extremely powerful, are not practical with molecules the size ofthe present invention. Molecular Dynamics simulations provide analternative that can be adapted efficiently to molecules envisioned inthe present invention. Key elements in determining conformationalenergies are strong electrostatic interactions (i.e., intramolecularhydrogen bonding) between adjacent or more distant monomers andrigidification caused by the backbone torsions or by bulky functionalgroups. In order to simulate these interactions in molecular mechanicscalculations the empirical parameters, i.e., a force field, must bedetermined for representative polymer backbones. Density functionaltheory (DFT) can be used to carry out ab initio calculations on smallmodel compounds that share the basic structural connectivity of thepolymer backbones and which will generate required torsional potentials.The procedure to carry out these computations is:

-   -   1. Select simple model compounds that share similar torsional        patterns with the target polymer backbones.    -   2. For each compound, perform a full geometric optimization at        the BLYP/6–31G(d) level of theory (multiple initial        configurations ensure the global minimum is obtained).    -   3. Calculate the single-point energy at the most stable geometry        obtained in step 2 above, using B3LYP/6–311G++(dp) or plane wave        CPMD.    -   4. Constrain a relevant torsion to a set angle and repeat steps        2 and 3.    -   5. Repeat step 4 for several angles; the torsional energy is        obtained by subtracting the non-bonded interactions.    -   6. Fit energies versus torsion angle to a cosine series whose        coefficients are the force field parameters.

After verifying the suitability of the force field by comparing computedpredictions of the structure and thermodynamic properties to moleculesthat have similar torsional patterns and for which experimental data areavailable, the fitted torsions are then combined with bond stretching,bending, one-four, van der Waals, and electrostatic potentials borrowedfrom the CHARMM (B. R. Brooks et al. J. Comp. Chem. 1983 4:187–217 andTraPPE (M. G. Martin and J. I. Siepmann, J. Phys. Chem B. 1999103:4508–17; C. D. Wick et al. J. Phys. Chem B. 2000 104:3093–3104)molecular dynamics force fields. To identify conformations that canadopt periodic folding patterns with polar groups and apolar groupslined up on the opposite sides. Initial structures can be obtained withthe Gaussian package (M. Frisch et al. Gaussian 98 (revision A.7)Gaussian Inc., Pittsburgh, Pa. 1998). Then, the parallelized plane-waveCar-Parrinello CP-MD (R, Car and M. Parrinello Phys. Rev. Lett. 198555:2471–2474) program, (cf. U. Röthlisberger et al. J. Chem. Phys. 19963692–3700) is used to obtain energies at the minimum and constrainedgeometries. The conformations of the polymers without side-chains can beinvestigated in the gas phase. Both MD and MC methods will be used tosample the conformations. The former is useful for global motions of thepolymer. With biasing techniques (J. I. Siepmann and D. Frenkel Mol.Phys. 1992 75:59–70; M. G. Martin and J. I. Siepmann J. Phys. Chem. B1999 103:4508–4517; T. J. H. Vlugt et al. Mol. Phys. 1998 94:727–733)the latter allows efficient sampling for polymers with multiple localminimum configurations that are separated by relatively large barriers.

The potential conformations are examined for positions to attach pendantgroups that will impart amphiphilic character to the secondarystructure. Polymers selected from the gas-phase studies with suitablebackbone conformations and with side-chains at the optimal positions tointroduce amphiphilicity will be further evaluated in a modelinterfacial system, n-hexane/water, chosen because it is simple andcheap for calculations while it mimics well the lipid/water bilayerenvironment. Polymer secondary structures that require inter-polymerinteractions can be identified by repeating the above-mentionedcalculations using a periodically repeated series of unit cells ofvarious symmetries (so called variable cell molecular dynamics or MonteCarlo technique) with or without solvent. The results of thesecalculations will guide the selection of candidates for synthesis.

An embodiment of the present is a computation technique to identifypolymer backbones which can produce facially amphiphilic polymers by:

-   -   (1) selecting a polymer backbones or scaffolds suitable for        regiospecific introduction of polar (P) and nonpolar (NP)        groups;    -   (2) determining parameters for a molecular mechanics force field        utilizing ab initio quantum mechanical calculations;    -   (3) calculating energetically accessible conformations of said        backbone using molecular dynamics or molecular mechanics        calculations;    -   (4) identifying energetically accessible conformations of said        backbone wherein the periodicity of a geometrical/conformational        repeat matches a sequence repeat;    -   (5) synthesizing monomers with polar and nonpolar substituents;    -   (6) synthesizing an antimicrobial polymer containing said        monomers by solution or solid-phase synthesis.

The facially amphiphilic polymers of the present invention can have asubstantial range in molecular weight. Facially amphiphilic moleculeswith molecular weights of about 0.8 kD to about 20 kD will be more proneto leach from the surface of the substrate. The facially amphiphilicpolymer may be attached to, applied on or incorporated into almost anysubstrate including but not limited to woods, paper, synthetic polymers(plastics), natural and synthetic fibers, natural and synthetic rubbers,cloth, glasses and ceramics by appropriate methods including covalentbonding, ionic interaction, coulombic interaction, hydrogen bonding orcross-linking. Examples of synthetic polymers include elasticallydeformable polymers which may be thermosetting or thermoplasticincluding, but not limited to polypropylene, polyethylene, polyvinylchloride, polyethylene terephthalate, polyurethane, polyesters, such aspolylactide, polyglycolide, rubbers such as polyisoprene, polybutadieneor latex, polytetrafluoroethylene, polysulfone and polyethylenesulfonepolymers or copolymers. Examples of natural fibers include cotton, wooland linen.

The polymers of the present invention thus provide a surface-mediatedmicrobicide that only kills organisms in contact with the surface.Moreover the polymers of the present invention are stable and retaintheir bioactivity for extended periods of time. Polymers bound to thesurface will not leach out of the surface into the environment.Specificity can be imparted for microbial cell walls which can providepolymers with reduced toxicity to birds, fish, mammals and other higherorganisms.

Any object that is exposed to or susceptible to bacterial or microbialcontamination can be treated with these polymers. These needs areparticularly acute in the health care and food industries. A growingconcern with preservatives has produced a need for new materials thatprevent microbiological contamination without including preservatives.The incidence of infection from food-borne pathogens is a continuingconcern and antimicrobial packaging material, utensils and surfaceswould be valuable. In the health care and medical device areas theutility of antimicrobial instruments, packaging and surfaces areobvious. Products used internally or externally in humans or animalhealth including, but not limited to, surgical gloves, implanteddevices, sutures, catheters, dialysis membranes, water filters andimplements, all can harbor and transmit pathogens. The polymers of thepresent invention can be incorporated into spinnable fibers for use inmaterials susceptible to bacterial contamination including fabrics,surgical gowns, and carpets. Ophthalmic solutions and contact lenseseasily become contaminated and cause ocular infections. Antimicrobialstorage containers for contact lens and cleaning solutions would be veryvaluable. Both pets and agronomic animals are exposed to and harbor avariety of infectious pathogenic organisms that can cause disease inanimals or humans.

Traditionally, monolayers have been created at air/water interfaces andtransferred to a variety of surfaces for chemical and structuralcharacterization, as documented in a large body of work dating back tothe seminal studies of Blodgett and Langmuir. Monolayers can bechemically bonded to solid supports, resulting in stable, uniformlypacked molecular layers that self-assemble by absorption. Typically,these Self-Assembled Monolayers (SAMS) are covalently tethered to solidsusing either alkylsiloxane or thiolate-gold linkages (for reviews see M.Mrksich, Cell Mol Life Sci, 1998 54:653–62; M. Mrksich, and G. M.Whitesides Ann Rev Biophys Biomol Struct, 1996 25:55–78).Alkylthiolate-gold linkages can be formed on the surface of gold byspontaneous absorption of a thiol or disulfide. Gold layers can bedeposited on most solid surfaces, providing great versatility.Alkylsiloxane monolayers can be prepared by reacting trialkoxysilanes ortrichlorosilanes with a silicon dioxide surface resulting in a monolayerof crosslinked siloxanes on the surface. Siloxane monolayers may beformed on any solid that contains surface silanol groups includingatomically smooth, surface-oxidized silicon wafers, glass and quartz.These two chemistries will allow amphiphilic polymers to be attached avariety of surfaces.

These amphiphilic polymers can incorporate linkers to allow the polymersto more efficiently interact with the environment around the solidsurface. Tethering chemistries that allow presentation of peptides andproteins in native conformations with minimal interaction with theunderlying substrate have been described. For examples, alkanethiols ofthe general form, HS—(CH₂)₁₁—(OCH₂—CH₂)_(n)—OH (denoted HS—C₁₁-E_(n),n=3–6), have now come into widespread use for studies of receptor/ligandinteractions (M. Mrksich Cell Mol. Life Sci.1998 54:653–62; M. Mrksichand G. M. Whitesides Ann. Rev. Biophys. Biomol. Struct.1996 25:55–78).Polyethylene glycol derived amino acids, e.g.Fmoc-NH—(CH₂—CH₂—O)₂)CH₂—COOH (Neosystems) have also been described Cyswill be appended to the N-terminus to act as a group that allowscoupling via its thiol, directly or through chemoselective ligation (T.W. Muir et al. Methods Enzymol. 1997 289:266–98; G. G. Kochendoerfer etal. Biochemistry 1999 38:11905–13). The thiol group serves to tether themolecule to gold surfaces, while the terminal hydroxyl and ethyleneglycol groups project towards solvent, presenting a hydrophilic surface.Attachment to siloxane and polyethylene surfaces have also beendescribed. (S. P. Massia and J. Stark J. Biomed. Mat. res. 200156:390–9; S. P. Massia and J. A. Hubbell J. Cell Biol. 1991114:1089–1100; S. P. Massia and J. A. Hubbell Anal. Biochem. 1990187:292–301; B. T. Houseman and M. Mrksich Biomaterials 2001 22:943–55).

Resin bound intermediates can easily be modified to incorporate linkers.Glass surfaces can be modified to allow reaction with the thiol groupsof the peptide by: (i) aminoalkylation of the glass surface by treatmentwith trimethoxysilylpropylamine; (ii) reaction of the amino groups witha bromoacetyl bromide or other heterobifunctional crosslinker groupscapable of also reacting with a thiol group. In the above example, weshow an amino surface in which we have introduced bromoacetyl groups forsubsequent reaction with peptide thiols. Alternatively, thiol-reactivemaleimides, vinyl-sulfones (Michael acceptors) may be incorporated usingcommercially available cross-linking agents. Alternatively, the surfaceamino groups may be converted to carboxylates by treatment with ananhydride, and then converted to thioesters under standard conditions.The resulting thioesters react facilely and with extremeregioselectivity with an N-terminal Cys residue. By incorporatingquantities of inactive “filler” molecule, e.g. one example which is notlimiting is a monofunctional thiol-terminated short chain polyethyleneglycol polymer with the reactive teathering group the molar ratio of theoligomer to the “filler” component, it should be possible tocontinuously vary the surface density of the polymers attached to asolid support.

An embodiment of the present invention is a process for producing anantimicrobial surface by attaching a antimicrobial facially amphiphilicpolymer to a surface comprising treating said surface with a firstchemically reactive group and reacting a facially amphiphilic polymerlinked to a second reactive group thereto.

Another embodiment of the present invention is a process for attaching afacially amphiphilic polymer to a surface wherein the solid surface istreated with a 1-(trialkoxysilyl)alkylamine and facially amphiphilicpolymer contains an activated carboxylic acid.

Yet another embodiment of the present invention is a process forattaching a facially amphiphilic polymer to a surface wherein the solidsurface is treated with a ω-(trialkoxysilyl)alkyl bromomethylacetamideand facially amphiphilic polymer contains a thiol.

Another embodiment of the present invention is a process for attaching afacially amphiphilic polymer to a surface wherein the solid surface istreated with a N-[ω-(trialkoxysilyl)alkyl]maleimide and faciallyamphiphilic polymer contains a thiol.

Still another embodiment of the present invention is a process forattaching a facially amphiphilic polymer to a surface wherein thesurface is gold and the facially amphiphilic polymer contains a thiol.

A variety of polymers are used in a host of medical applications whichrequire sterile surfaces. Catheters, like venous or urinary cathetersare cause serious infections. Polyurethane based tubing is by far themajor source of commercial catheter tubing. Amphiphilic polymers can beincorporated into polyurethane and other polymers using pre- and postmanufacture techniques. The advantage of pre-manufacture incorporationis simpler modification strategies and dispersion of the antimicrobialagent throughout the tubing materials. Tubing manufacturing is typicallyan extrusion process in which pellets of polyurethane are heated andpressed through a dye producing tubing of the desired diameter. Thethermal stability of urethane bonds is very similar to amide and ureabonds again suggesting that thermal processed conditions should not be aproblem. For the pre-manufacture approach, designed antimicrobialpolymers are added to the original polyurethane pellets before extrusionresulting in a uniform dispersion throughout the extruded polymer.

Post-manufacture modifications are also possible although in this casethe antimicrobial polymer will only be present on the surface of thetubing. However, since catheters have a minimal life cycle it is likelythat surface treatment will render the materials sufficiently sanitaryfor their application. There are a variety of methods one can use tomodify polymeric surfaces (E. Piskin J. Biomat. Sci.-Polymer Ed. 19924:45–60). The most common technique to covalent attach a amphiphilicpolymer to the surface relies on irradiation to produce free radicalsthat form covalent bonds between the polymer and active surface agent.Unfortunately, this process is completely random with no control overorientation or functional group attachment to the surface.Alternatively, photo or chemical oxidation of the polyurethane surfacecan create carboxylic acid or alcohol functionality which will bereactive toward these antimicrobial polymers (the cationic side chainsor cationic end groups). The most common technique for surface oxidationis plasma etching (E. Piskin loc. cit.; S. H. Hsu and W. C. Chen,Biomaterials 2000 21:359–67) although ozone can also be used. Afteroxidation, the surface is treated with a bifunctional epoxide followedby addition of the cationic antimicrobial polymer which can react withthe epoxide.

Microbial growth in paint and on the surface of paint films also remainsan unsolved problem. This can occur in the wet formulated paint or bymicrobial growth on the dried surface. The paint industry currently useseither isothiazolones or “formaldehyde releasers” for wet paintprotection from microbes (G. Sekaran et al. J. Applied Polymer Sci. 200181:1567–1571; T. J. Kelly et al. Environ. Sci. Technol. 1999 33:81–88;M. Sondossi et al. International Biodeterioration & Biodegradation 199332:243–61). Both of these products are harmful to human beings and greatlengths and expense are taken at the factory to limit employee exposure;however, there is no viable alternative currently for the industry.Isothiazolones are used mainly for their effectiveness againstPseudomonas aeruginosa and that the antimicrobial polymers discussed inpreliminary data are active against this strain.

Any object that is exposed to or susceptible to bacterial or microbialcontamination can be treated with these polymers. These needs areparticularly acute in the health care and food industries. A growingconcern with preservatives has produced a need for new materials thatprevent microbiological contamination without including preservatives.The incidence of infection from food-borne pathogens is a continuingconcern and antimicrobial packaging material, utensils and surfaceswould be valuable. In the health care and medical device areas theutility of antimicrobial instruments, packaging and surfaces areobvious. Products used internally or externally in humans or animalhealth including, but not limited to, surgical gloves, implanteddevices, sutures, catheters, dialysis membranes, water filters andimplements, all can harbor and transmit pathogens. The polymers of thepresent invention can be incorporated into spinnable fibers for use inmaterials susceptible to bacterial contamination including fabrics,surgical gowns, and carpets. Ophthalmic solutions and contact lenseseasily become contaminated and cause ocular infections. Antimicrobialstorage containers for contact lens and cleaning solutions would be veryvaluable. Both pets and agronomic animals are exposed to and harbor avariety of infectious pathogenic organisms that can cause disease inanimals or humans.

An embodiment of the current invention is a antimicrobial compositioncomprising a facially amphiphilic polymer and a composition selectedform the group consisting of paint, coatings, lacquer, varnish, caulk,grout, adhesives, resins, films, cosmetic, soap and detergent.

Another embodiment of the present invention is an improved catheter, theimprovement comprising incorporating or attaching a facially amphiphilicpolymer therein or thereto.

Yet another embodiment of the present invention is an improved contactlens, the improvement comprising incorporating or attaching anamphiphilic polymer therein or thereto.

An embodiment of the present invention is improved plastic devices forthe hospital and laboratory the improvement comprising incorporating orattaching a facially amphiphilic polymer therein or thereto.

A further embodiment of the present invention is an improved woven andnonwoven fabrics for hospital use the improvement comprising theincorporating or attaching a facially amphiphilic polymer therein orthereto.

The following examples will serve to further typify the nature of thisinvention but should not be construed as a limitation in the scopethereof, which scope is defined solely by the appended claims.

EXAMPLE 1 Polyamide FIG. 6 XIa

2,6-Dinitro-4-t-butyl-phenyl (4-methyl)-benzenesulfonate (11)

2,6-dinitro-4-t-butyl-phenol (80 mmol; 10) and tosyl chloride (80 mmol)were dissolved in 300 ml CH₂Cl₂. Diisopropylethylamine (DIEA, 80 mmol)was added to the solution. The mixture was stirred at room temperaturefor 2 hours. The solution was washed with 10% citric acid, saturatedaqueous NaCl (sat. NaCl), and dried with MgSO₄. The solvent was removedunder reduced pressure, and the product was obtained as a bright yellowsolid in quantitative yield. ¹H NMR (500 MHz, CDCl₃): δ=8.12 (s, 2H),7.80 (d, 2H), 7.40 (d, 2H), 2.51(s, 3H), 1.41 (s, 9H). ESI-MS: m/z:417.2 (M+Na⁺).

2,6-Dinitro-4-t-butyl-1-(2-t-butoxycarbonylaminoethyl)-sulfanylbenzene(12).

Compound 11 (13 mmol), 2-Boc-aminoethanthiol (16 mmol) and DIEA(13 mmol)were dissolved in 50 ml chloroform. The solution was stirred undernitrogen for 12 hours. The solution was washed with 0.5 M NaOH, 10%citric acid, sat. Na₂CO₃ and sat. NaCl, and dried with MgSO₄. Thesolution volume was reduced to 15 ml by rotary evaporation. Afteraddition of 80 ml hexane the product crystallized as a bright yellowsolid in. 94% yield. ¹H NMR (500 MHz, CDCl₃): δ 7.81 (s, 2H), 4.87 (s,1H), 3.31 (t, 2H), 3.10 (t, 2H), 1.44 (s, 9H), 1.39 (s, 9H). ESI-MS:m/z: 422.4 (M+Na⁺).

2,6-Diamino-4-t-butyl-1-(2-t-butoxycarbonylaminoethyl)sulfanylbenzene(13)

Dinitro compound 12 (20 mmol) and sodium acetate (200 mmol) were addedto 50 ml EtOH. The mixture was heated to 78° C., and the solid dissolvedcompletely. Stannous chloride dihydrate (200 mmol) was added to thesolution, and the reaction mixture was stirred at 78° C. for 35 minutes.After removal of solvent under reduced pressure, the residue wasdissolved in 800 ml EtOAc, and washed with 40% KCO₃. The organic phasewas dried, evaporated and the residue column chromatographed (SiO₂) andeluted with a gradient of CH₂Cl₂/MeOH from 100:1 to 95:5 to produce 13in 93% yield. ¹H NMR (500 MHz, CDCl₃): δ 6.21 (s, 2H), 5.41 (s, 1H),4.35 (br, 4H), 3.21 (t, 2H), 2.75 (t, 2H), 1.35 (s, 9H), 1.24 (s, 9H).ESI-MS: m/z: 340.5 (MH⁺).

General Method of Polymerization.

Diamine 13 (0.1 mmol) was dissolved in 3 ml DMF. Isophthaloyl dichloride(0.1 mmol), triethylamine (0.2 mmol) ) and N,N-dimethylethylenediamine(0.2/n mmol)were added while stirring. The mixture was stirred undernitrogen for 18 hours. After the volume of solvent was reduced to 1 ml,water was added to precipitate the polymer. The polymer was collectedand dried under vacuum. The Boc group was removed by treatment withtrifluoroacetic acid (TFA, 3 ml) for 1 hour. The deprotected polymer wasdried under vacuum overnight.

EXAMPLE 2 Solid Phase Synthesis of Oligomers XIb and XIc (FIG. 6)

Fmoc-PAL-PEG-resin (0.1 mmol) was swelled in DMF; then the Fmoc wasremoved with 20% piperidine in DMF for 20 min. The oligomer was thenbuilt up by alternately coupling 10 equivalents of isophthalic acid ordiamine 10. In each case the couplings were carried out in DMF using 10equivalents each of2-(1H-benzotriazole-1-yl)-1,1,3,3,-tetramethyluroniumhexafluorophosphate (HBTU) and N-hydroxybenzotriazole hydrate (HOBt),and 20 equivalents of DIEA for 24 hours at room temperature. Theoligomers were cleaved from the resin by treatment with TFA/anisole(95:5) for 1 hour. Pure oligomers were obtained by HPLC on a reversephase C4 column, with a linear gradient from 30% to 80% solvent B in 50minutes (solvent A, 0.1% TFA in water; solvent B, acetonitrile/water/TFA900:99:1). MALDI-TOF MS: XIb: 756.5 (M+H⁺), XIc: 1125.6.(M+H⁺).

EXAMPLE 3 General Method for Amide Polymerization

An oven-dried flask is charged with diamine dissolved indimethylsulfoxide (DMSO). To this solution is added an equimolarquantity of the diacid chloride which is freshly prepared by stirringthe dicarboxylic acid with excess thionyl chloride for 2 hr prior toaddition to the diamine solution. A catalytic amount of4-dimethylaminopyridine and four-fold molar excess of triethylamine areadded to the stirring mixture. The reaction is stirred at roomtemperature overnight under positive N₂ pressure. The DMSO solution ispoured into water and the solid polymer is recovered by filtration. Thedegree of polymerization is controlled by the addition of various molaramounts of a monofunctional amine. The molar amount of themonofunctional amine is determined by the Flory equation (G. Odian,Principles of Polymerization, John Wiley & Sons, Third Edition (1991)p.78–82).

EXAMPLE 4 General Method for Urea Polymerization

A dried flask is charged with equal molar ratios of the diamine and thediisocyanate in DMSO. The reaction is stirred at room temperatureovernight under positive N₂ pressure. The reaction is poured into wateror ether and the solid polymer is recovered by filtration. The degree ofpolymerization is controlled by the addition of various molar amounts ofa monofunctional amine. The molar amount of the monofunctional amine isdetermined by the Flory equation.

EXAMPLE 5 Antimicrobial Assays

The inhibition studies will be carried out in suspension using BHImedium inoculated with bacteria (10⁶ CFU/ml) in a 96-well format. Astock solution of the polymers was prepared DMSO/water and used toprepare a ten fold dilution series. Minimal inhibitory concentrations(MIC) were obtained by incubating the compounds with the bacteria for 18hours at 37° C., and measuring cell growth by monitoring at 590 nm.Antibacterial data is described in FIGS. 10 and 11.

EXAMPLE 6 Hemolytic Activity

The toxicity of the polymers to mammalian cells was evaluated with humanblood, anticoagulated with 0.1 volume of sodium citrate, obtained fromhealthy volunteers. Washed erythrocytes are suspended in either HEPESbuffer, pH 7.4, containing 1 mM Mg²⁺ and 1 mM Ca²⁺ or in heated andunheated autologous serum obtained from clotted blood. Red cellagglutination will be evaluated microscopically and red cell lysis willbe evaluated by measuring the amount of released hemoglobinspectroscopically. The effect of polymers on platelet function will bestudied by adding increasing concentrations of polymer tocitrate-anticoagulated platelet-rich plasma. Platelet aggregation andsecretion will then be studied in a lumi-aggregometer (Chrono-Log).

All references cited in the application are hereby incorporated in theirentirety into this specification. Numerous modifications and alternativeembodiments of the invention will be apparent to those skilled in theart in view of the foregoing description. Accordingly, this descriptionis to be construed as illustrative only and is for the purpose ofteaching those skilled in the art the best mode of carrying out theinvention. Details of the structure may be varied substantially withoutdeparting from the spirit of the invention and the exclusive use of allmodifications which come within the scope of the appended claim isreserved.

1. A polymer or oligomer comprising a compound of formula I

wherein: x is NR³, O, or S; y is C═O, C═S, O═S═O, or —C(═O)C(═O)—; andR³ is hydrogen, methyl or ethyl; either both A and B are independentlyoptionally substituted o-, m-, p-phenylene, or optionally substitutedheteroarylene wherein (i) A and B are both substituted with a polar (P)group and a nonpolar (NP) group, (ii) one of A and B is substituted witha polar (P) group and a nonpolar (NP) group and the other of A and B issubstituted with neither a polar nor a nonpolar group, or (iii) one of Aor B is substituted with a polar (P) group and the other of A or B issubstituted with a nonpolar (NP) group; or, one of A and B is o-, m-,p-phenylene or heteroarylene and the other of A and B is a C₃ to C₈cycloalkyl or (CH₂)_(q) where q is 1 to 7 wherein (i) one of A or B isoptionally substituted by one or more polar (P) group(s) and the otherof A or B is optionally substituted with one or more nonpolar (NP)group(s), or (ii) A is substituted with a polar (P) group and a nonpolar(NP) group and B is a C₃ to C₈ cycloalkyl or (CH₂)_(q) where q is 1 to 7and B is optionally independently substituted with one or more polar (P)or nonpolar (NP) group; R¹ is (i) -y-C and R² is OH or NH₂ wherein C isselected from the group consisting of C₁–C₆ alkyl, C₁–C₆ haloalkyl,vinyl, 2-propenyl, H-x-(CH₂)_(p)—, (C₁–C₆-alkoxy)C(═O)(CH₂)_(p)—, C₁–C₆alkoxy, benzyloxy, t-butoxy, pyridine and phenyl said pyridine or phenyloptionally substituted with 1 or 2 substituents independently selectedfrom the group consisting of halo, nitro, cyano, C₁–C₆ alkoxy, C₁–C₆alkoxycarbonyl, and benzyloxycarbonyl; or, (ii) is H and R² is-x-(CH₂)_(p)—W wherein x is as defined above and p is as defined belowand W is H, N-maleimide or V as defined below, or (iii) -y-C and R² is-x-(CH₂)_(p)—W; or (iv) R¹ and R² together are a single bond; NP is anonpolar group independently selected from R⁴ or —U—(CH₂)_(p)—R⁴ whereinR⁴ is selected from the group consisting of hydrogen, C₁–C₁₀ alkyl,C₁–C₆ haloalkyl, C₃–C₁₈ branched alkyl, C₃–C₈ cycloalkyl, and monocyclicor polycyclic phenyl optionally substituted with one or more C₁–C₄alkyl, C₁–C₄ alkoxy or halo groups and monocyclic or polycyclicheteroaryl optionally substituted with one or more C₁–C₄ alkyl, C₁–C₄alkoxy, or halo groups and U and p are as defined below; P is a polargroup selected from the group consisting of IIIa, hydroxyethoxymethyl,methoxyethoxymethyl and polyoxyethylene,—U—(CH₂)_(p)—V  (IIIa)  wherein: U is absent or selected from the groupconsisting of O, S, S(═O), S(═O)₂, NH, —C(═O)O—, —C(═O)NH—, —C(═O)S—,—C(═S)NH—, —S(═O)₂NH—, and C(═NO—) wherein groups with two chemicallynonequivalent termini can adopt both possible orientations; V isselected from the group consisting of amino, hydroxyl, thio, C₁–C₆alkylamino, C₁–C₆ dialkylamino, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, amidine,guanidine, semicarbazone, C₁–C₆ alkoxycarbonyl, basic heterocycle, andphenyl optionally substituted with an amino, C₁–C₆ alkylamino, C₁–C₆dialkylamino and lower acylamino optionally substituted with one or moreamino, lower alkylamino or lower dialkylamino; and the alkylene chain isoptionally substituted with an amino or hydroxyl group or unsaturated; pis independently 0 to 8; and m is 2 to at least about
 500. 2. Thepolymer or oligomer of claim 1, wherein said polymer or oligomercomprises a compound of formula VII

wherein: one of R⁹ or R¹⁰ and R¹¹ is a polar (P) group and the other ofR⁹ or R¹⁰ and R¹¹ is a nonpolar (NP) group; P is a polar group selectedfrom the group consisting of IIIb, hydroxyethoxymethyl,methoxyethoxymethyl and polyoxyethylene,—(CH₂)_(p)—V  (IIIb)  wherein: V is selected from the group consistingof amino, hydroxyl, C₁–C₆ alkylamino, C₁–C₆ dialkylamino,NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, amidine, guanidine, semicarbazone,imidazole, piperidine, piperazine, 4-alkylpiperazine and phenyloptionally substituted with an amino, C₁–C₆ alkylamino, C₁–C₆dialkylamino and lower acylamino optionally substituted with one or moreamino, lower alkylamino or lower dialkylamino; and, the alkylene chainis optionally substituted with an amino or hydroxyl group; p isindependently 0 to 8; and m is 2 to at least about
 30. 3. The polymer oroligomer of claim 2, wherein said polymer or oligomer comprises acompound of formula IX

wherein: one of R⁹ or R¹¹ is either a polar (P) group or a nonpolar (NP)group and the other of R⁹ or R¹¹ is the other of a polar (P) group or anonpolar (NP) group; NP is —(CH₂)_(p)—R⁴ wherein R⁴ is selected from thegroup consisting of hydrogen, C₁–C₄ alkyl, C₃–C₁₂ branched alkyl, C₃–C₈cycloalkyl, and phenyl optionally substituted with one or more C₁–C₄alkyl group, C₁–C₄ alkoxy or halo groups and heteroaryl optionallysubstituted with one or more C₁–C₄ alkyl group, C₁–C₄ alkoxy or halogroups and p is as defined below; P is a polar group selected from thegroup consisting of IIIb, hydroxyethoxymethyl, methoxyethoxymethyl andpolyoxyethylene,—(CH₂)_(p)—V  (IIIb)  wherein: V is selected from the group consistingof amino, hydroxyl, C₁–C₆ alkylamino, C₁–C₆ dialkylamino,NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, amidine, guanidine, semicarbazone,imidazole, piperidine, piperazine, 4-alkylpiperazine and phenyloptionally substituted with an amino, C₁–C₆ alkylamino, C₁–C₆dialkylamino and lower acylamino optionally substituted with one or moreamino, lower alkylamino or lower dialkylamino; the alkylene chain isoptionally substituted with an amino or hydroxyl group; and p isindependently 0 to
 8. 4. The polymer or oligomer of claim 3, wherein R⁹is a polar side chain of a natural amino acid and R¹¹ is selected fromthe group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyliso-butyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, sec-pentyl, andbenzyl.
 5. The polymer or oligomer of claim 3, wherein R⁹ is a nonpolarside chain of a natural amino acid and R¹¹ is a polar group selectedfrom the group consisting of IIIb, hydroxyethoxymethyl,methoxyethoxymethyl and polyoxyethylene,—(CH₂)_(p)—V  (IIIb) wherein: V is selected from the group consisting ofamino, hydroxyl, C₁–C₆ alkylamino, C₁–C₆ dialkylamino, NH(CH₂)_(p)NH₂,N(CH₂CH₂NH₂)₂, amidine, guanidine, semicarbazone, imidazole, piperidine,piperazine, 4-alkylpiperazine and phenyl optionally substituted with anamino, C₁–C₆ alkylamino, C₁–C₆ dialkylamino and lower acylaminooptionally substituted with one or more amino, lower alkylamino or lowerdialkylamino; and p is independently 0 to
 8. 6. The polymer or oligomerof claim 1, wherein: x is NH and y is C═O or CS; A and B areindependently optionally substituted o-, m-, or p-phenylene,2,5-thiophenylene or 2,5-pyrrolene; NP is a nonpolar group independentlyselected from R⁴ or —U—(CH₂)_(p)—R⁴ wherein R⁴ is selected from thegroup consisting of hydrogen, C₁–C₄ alkyl, C₃–C₁₂ branched alkyl, C₃–C₈cycloalkyl, phenyl optionally substituted with one or more C₁–C₄ alkylgroups, C₁–C₄ alkoxy or halo groups, and heteroaryl optionallysubstituted with one or more C₁–C₄ alkyl groups, C₁–C₄ alkoxy or halogroups, and U and p are as defined below; P is a polar group selectedfrom the group consisting of IIIa, hydroxyethoxymethyl,methoxyethoxymethyl and polyoxyethylene,—U—(CH₂)_(p)—V  (IIIa) wherein: U is absent, O, S, SO, SO₂, or NH; V isselected from the group consisting of amino, hydroxyl, C₁–C₆ alkylamino,C₁–C₆ dialkylamino, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, amidine, guanidine,semicarbazone, imidazole, piperidine, piperazine, 4-alkylpiperazine andphenyl optionally substituted with an amino, C₁–C₆ alkylamino, C₁–C₆dialkylamino and lower acylamino optionally substituted with one or moreamino, lower alkylamino or lower dialkylamino; and, the alkylene chainis optionally substituted with an amino or hydroxyl group; p isindependently 0 to 8; and m is 2 to at least about
 500. 7. The polymeror oligomer of claim 1, wherein: x is NR³, R³ is hydrogen, and y is C═Oor CS; A and B are independently optionally substituted o-, m-, orp-phenylene; NP a nonpolar group independently selected from R or—U—(CH₂)_(p)—R⁴ wherein R⁴is selected from the group consisting ofhydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,sec-butyl, tert-butyl, n-pentyl, iso-pentyl, and sec-pentyl, and U and pare as defined below; P is a polar group U—(CH₂)_(p)—V wherein U isabsent or selected from the group consisting of O and S, and V isselected from the group consisting of amino, lower alkyl amino, lowerdialkylamino, imidazole, guanidine, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂,pyridine, piperidine, piperazine, and 4-alkylpiperazine; p isindependently 0 to 8; and m is 2 to at least about
 500. 8. The polymeror oligomer of claim 7, wherein: x is NR³, y is CO, and R³ is hydrogen;A and B are m- or p-phenylene wherein (i) A is substituted at the2-position with a polar (P) group and B is substituted at the 5-positionwith a nonpolar (NP) group, (ii) A is substituted at the 2-position witha polar (P) group and at the 5-position with a nonpolar (NP) group and Bis substituted at the 2-position with a nonpolar (NP) group and at the5-position with a polar (P) group, or (iii) A is substituted at the2-position with one of a polar (P) or nonpolar (NP) group and B issubstituted at the 2-position with the other of a nonpolar (NP) or apolar (P) group; NP is a nonpolar group independently selected from R⁴or —U—R⁴ wherein R⁴ is selected from the group consisting of methyl,ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,n-pentyl, iso-pentyl, and sec-pentyl, and U and p are as defined below;p is independently 0 to 8; and m is 2 to at least about
 500. 9. Thepolymer or oligomer of claim 8, wherein said polymer or oligomercomprises a compound of formula XII

 wherein: NP is a nonpolar group independently selected from the groupconsisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,sec-butyl, tert-butyl, n-pentyl, iso-pentyl, and sec-pentyl, and U and pare as defined below; P is a polar group U—(CH₂)_(p)—V wherein U isselected from the group consisting of O, S, and no atom and V isselected from the group consisting of amino, lower alkyl amino, lowerdialkylamino, imidazole, guanidine, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂,piperidine, piperazine, and 4-alkylpiperazine; p is independently 0 to8; and m is 2 to at least about
 30. 10. The polymer or oligomer of claim8, wherein said polymer or oligomer comprises a compound of formula XIV,

wherein: NP is a nonpolar group independently selected from R⁴ or —U—R⁴wherein R⁴ is selected from the group consisting of methyl, ethyl,n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,n-pentyl, iso-pentyl, and sec-pentyl, and U and p are as defined below;P is a polar group U—(CH₂)_(p)—V wherein U is selected from the groupconsisting of O, S, and no atom and V is selected from the groupconsisting of amino, lower alkyl amino, lower dialkylamino, imidazole,guanidine, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, piperidine, piperazine, and4-alkylpiperazine; p is independently 0 to 8; and m is 2 to at leastabout
 30. 11. The polymer or oligomer of claim 1, wherein: x is NR³, yis CO, and R³ is hydrogen; A and B are o-phenylene wherein A issubstituted at the 5-position with a polar (P) group and B issubstituted at the 5-position with a nonpolar (NP) group; NP is anonpolar group independently selected from R⁴ or —U—R⁴ wherein R⁴selected from the group consisting of methyl, ethyl, n-propyl,iso-propyl, iso-butyl, n-butyl, sec-butyl, tert-butyl, n-pentyl,iso-pentyl, and sec-pentyl, and U and p are as defined below; P is apolar group U—(CH₂)_(p)—V wherein U is selected from the groupconsisting of O, S, and no atom and V is selected from the groupconsisting of amino, lower alkyl amino, lower dialkylamino, imidazole,guanidine, NH(C₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, pyridine, piperidine,piperazine, and 4-alkylpiperazine; p is independently 0 to 8; and m is 2to at least about
 500. 12. The polymer or oligomer of claim 11, whereinsaid polymer or oligomer comprises a compound of formula XIII:

wherein: NP is a nonpolar group independently selected from the groupconsisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,sec-butyl, tert-butyl, n-pentyl, iso-pentyl, and sec-pentyl, and U and pare as defined below; P is a polar group (CH₂)_(p)—V wherein V isselected from the group consisting of amino, lower alkyl amino, lowerdialkylamino, guanidine, piperazine, and 4-alkylpiperazine; p isindependently 0 to 8; and m is 2 to at least about
 30. 13. The polymeror oligomer of claim 11, wherein said polymer or oligomer comprises acompound of formula XV:

wherein either R¹² and R¹⁴ are independently polar (P) groups and R¹³and R¹⁵ are independently nonpolar (NP) groups substituted at one of theremaining unsubstituted carbon atoms, or R¹² and R¹⁴ are independentlynonpolar (NP) groups and R¹³ and R¹⁵ are independently polar (P) groups;NP is a nonpolar group independently selected from R⁴ or —U—R⁴ whereinR⁴ is selected from the group consisting of methyl, ethyl, n-propyl,iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl,iso-pentyl, and sec-pentyl, and U is defined below; P is a polar groupU—(CH₂)_(p)—V wherein U is selected from the group consisting of O and Sand V is selected from the group consisting of amino, lower alkyl amino,lower dialkylamino, guanidine, pyridine, piperazine, and4-alkylpiperazine; p is independently 0 to 8; and m is 2 to at leastabout
 30. 14. A polymer or oligomer comprising a compound of formula II

wherein: x and y can be (i) taken independently wherein x is NR³, O, S,(CR⁷R⁸)NR³, (CR⁷R⁸)O, or (CR⁷R⁸)S, y is C═O, C═S, O═S═O, —C(═O)C(═O)—,(CR⁵R⁶)C═O or (CR⁵R⁶)C═S, and R³ is hydrogen, methyl or ethyl; or, (ii)taken together to be pyromellitic diimide; and R⁵ and R⁶ together are(CH₂)₂NR¹²(CH₂)₂ and R¹² is selected from the group consisting ofhydrogen, C(═N)CH₃ and C(═NH)—N2 and R⁷ and R⁸ together are (CH₂)_(p)wherein p is as defined below; both A and B are independently optionallysubstituted o-, m-, p-phenylene, or optionally substituted heteroarylenewherein (i) A and B are both substituted with a polar (P) group and anonpolar (NP) group, (ii) one of A and B is substituted with a polar (P)group and a nonpolar (NP) group and the other of A and B is substitutedwith neither a polar nor a nonpolar group, or (iii) one of A or B issubstituted with a polar (P) group and the other of A or B issubstituted with a nonpolar (NP) group; R¹ is (i) -y-B-y-R² and R² is-x-(CH₂)_(p)—W, wherein x is as defined above and W is hydrogen, phenyloptionally substituted with up to three substituents selected from thegroup consisting of halogen, C₁–C₄ alkyl, C₁–C₄ alkoxy, and carboxyl,N-maleimide, or V as defined below, and p is as defined below; or, (ii)R¹ and R² together are a single bond; NP is a nonpolar group anindependently selected from R⁴ or —U—(CH₂)_(p)—R⁴ wherein R⁴ is selectedfrom the group consisting of hydrogen, C₁–C₂ alkyl, C₁–C₆ haloalkyl,C₃–C₁₈ branched alkyl, C₃–C₈ cycloalkyl, monocyclic or polycyclic phenyloptionally substituted with one or more C₁–C₄ alkyl, C₁–C₄ alkoxy orhalo groups, and monocyclic or polycyclic heteroaryl optionallysubstituted with one or more C₁–C₄ alkyl, C₁–C₄ alkoxy, or halo groups,and U and p are as defined below; P is a polar group selected from thegroup consisting of IIIa, hydroxyethoxymethyl, methoxyethoxymethyl andpolyoxyethylene,—U—(CH₂)_(p)—V  (IIIa)  wherein, U is absent or selected from the groupconsisting of O, S, S(═O), S(═O)₂, NH, —C(═O)O—, —C(═O)NH—, —C(═O)S—,—C(S)NH—, —S(═O)₂NH—, and C(═NO—) wherein groups with two chemicallynonequivalent termini can adopt both possible orientations; V isselected from the group consisting of amino, hydroxyl, thio, C₁–C₆alkylamino, C₁ –C₆ dialkylamino, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, amidine,guanidine, semicarbazone, C₁–C₆ alkoxycarbonyl, basic heterocycle, andphenyl optionally substituted with an amino, C₁–C₆ alkylamino, C₁–C₆dialkylamino; and lower acylamino optionally substituted with one ormore amino, lower alkylamino or lower dialkylamino; and the alkylenechain is optionally substituted with an amino or hydroxyl group orunsaturated; p is independently 0 to 8; and m is 2 to at least about500.
 15. The polymer or oligomer of claim 14, wherein: x=NH and y=CO; Aand B are m- or p-phenylene wherein (i) A is substituted at the2-position with a polar (P) group and B is substituted at the 5-positionwith a nonpolar (NP) group, or (ii) A is substituted at the 2-positionwith a polar (P) group and at the 5-position with a nonpolar (NP) groupand B is either substituted at the 2- position with a nonpolar (NP)group and at the 5-position with a polar (P) group or B isunsubstituted; NP is a nonpolar group independently selected from R⁴ or—U—(CH₂)_(p)—R⁴ wherein R⁴ is selected from the group consisting ofmethyl, ethyl, n-propyl, iso-propyl, iso-butyl, sec-butyl, tert-butyl,iso-pentyl, and sec-pentyl, and U and p are as defined below; P is apolar group U—(CH₂)_(p)—V wherein U is absent or selected from the groupconsisting of O and S, and V is selected from the group consisting ofamino, lower alkyl amino, lower dialkylamino, imidazole, guanidine,NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, piperidine, and 4-alkylpiperazine; p isindependently 0 to 8; and m is 2 to at least about
 500. 16. The polymeror oligomer of claim 15, where A is an optionally substituted1,3-diaminobenzene and B is an optionally substituted iso-phthalic acid.17. The polymer or oligomer of claim 15, wherein said polymer oroligomer comprises a compound of formula XI

wherein: R⁴ is selected from the group consisting of methyl, ethyl,n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,n-pentyl, iso-pentyl, and sec-pentyl; U is O or S; V is amino, loweralkyl amino, lower dialkylamino, or guanidine; p is independently 0–8;and m is 2 to at least about
 30. 18. The polymer or oligomer of claim15, wherein said polymer or oligomer comprises a compound of formula XVI

wherein: either R¹² and R¹⁴ are independently polar (P) groups and R¹³and R¹⁵ are independently nonpolar (NP) groups substituted at one of theremaining unsubstituted carbon atoms, or R¹² and R¹⁴ are independentlynonpolar (NP) groups and R¹³ and R¹⁵ are independently polar (P) groups;NP is a nonpolar group independently selected from R⁴ or —U—R⁴ where R⁴is selected from the group consisting of methyl, ethyl, n-propyl,iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl,iso-pentyl, and sec-pentyl, and U is as defined below; P is a polargroup U—(CH₂)_(p)—V wherein U is absent or selected from the groupconsisting of O and S, and V is selected from the group consisting ofamino, lower alkyl amino, lower dialkylamino, imidazole, guanidine,NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, piperidine, and 4-alkylpiperazine; U is Oor S; V is amino, lower alkyl amino, lower dialkylamino, or guanidine; pis independently 0 to 8; and m is 2 to at least about
 30. 19. Thepolymer or oligomer of claim 15, wherein said polymer or oligomercomprises a compound of formula XX

wherein j is independently 0 or 1, R⁵ and R⁶ together are (CH₂)₂NH(CH₂)₂and R⁷ and R⁸ together are (CH₂)_(p) wherein p is 4 to
 6. 20. A polymeror oligomer comprising a compound of formula IV

wherein: x is NR³ or NHNH; y is NR³, NHNH, S or O; and R³ is hydrogen,methyl or ethyl; z is C═O, —(C═O)C(═O)—, C═S or O═S═O; A and B areindependently optionally substituted o-, m-, p-phenylene or optionallysubstituted heteroarylene wherein (i) A and B are both substituted witha polar (P) group and a nonpolar (NP) group, (ii) one of A and B issubstituted with a polar (P) group and a nonpolar (NP) group and theother of A and B is substituted with neither a polar nor a nonpolargroup, (iii) one of A or B is substituted with one or two polar (P)group(s) and the other of A or B is substituted with one or two nonpolar(NP) group(s), or (iv) A is substituted at the ₂-position with a polar(P) group and at the 5-position with a nonpolar (NP) group and B isunsubstituted; R¹ is (i) —B-y-R² and R² is -x-(CH₂)_(p)—W wherein x isas defined above and W is hydrogen, pyridine and phenyl said pyridine orphenyl optionally substituted with 1 or 2 substituents independentlyselected from the group consisting of halo, nitro, cyano, C₁–C₆ alkoxy,C₁–C₆ alkoxycarbonyl, and benzyloxycarbonyl; (ii) R¹ is H and R is-x-(CH₂)_(p)—V, or (iii) R¹ and R² together are a single bond; NP is anonpolar group independently selected from R⁴ or —U—(CH₂)_(p)—R⁴ whereinR⁴ is selected from the group consisting of C₁–C₈ alkyl, C₁–C₆haloalkyl, C₃–C₁₈ branched alkyl, C₃–C₈ cycloalkyl, monocyclic orpolycyclic phenyl optionally substituted with one or more C₁–C₄ alkyl orhalo groups, and monocyclic or polycyclic heteroaryl optionallysubstituted with one or more C₁–C₄ alkyl or halo groups, and U and p areas defined below; P is a polar group selected from the group consistingof IIIa, hydroxyethoxymethyl, methoxyethoxymethyl and polyoxyethylene,—U—(CH₂)_(p)—V  (IIIa)  wherein: U is absent or selected from the groupconsisting of O, S, S(═O), S(═O)₂, NH, —C(═O)O—, —C(═O)NH—, —C(═O)S—,—C(═S)NH—, —S(═O)₂NH—, and C(═NO—) wherein groups with two chemicallynonequivalent termini can adopt both possible orientations; V isselected from the group consisting of amino, hydroxyl, C₁–C₆ alkylamino,dialkylamino, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, amidine, guanidine,semicarbazone, basic heterocycle, and phenyl optionally substituted withan amino, C₁–C₆ alkylamino, C₁–C₆ dialkylamino and lower acylaminooptionally substituted with one or more amino, lower alkylamino or lowerdialkylamino; and the alkylene chain is optionally substituted with anamino or hydroxyl group or optionally unsaturated; p is independently 0to 8; and m is 2 to at least about
 500. 21. The polymer or oligomer ofclaim 20, wherein: x and y are NR³, z is C═O or C═S, and R³ is hydrogen;A and B are independently optionally substituted o-, m-, or p-phenylene;NP is a nonpolar group independently selected from R⁴ or —U—(CH₂)_(p)—R⁴wherein R⁴ is selected from the group consisting of hydrogen, C₁–C₄alkyl, C₃–C₁₂ branched alkyl, C₃–C₈ cycloalkyl, phenyl optionallysubstituted with one or more C₁–C₄ alkyl groups and heteroaryloptionally substituted with one or more C₁–C₄ alkyl groups, and U and pare as defined below; P is a polar group selected from the groupconsisting of IIIa, hydroxyethoxymethyl, methoxyethoxymethyl orpolyoxyethylene,—U—(CH₂)_(p)—V  (IIIa)  wherein: U is O, S, S(═O), S(═O)₂, NH, orabsent; V is selected from a group consisting of amino, hydroxyl, C₁–C₆alkylamino, dialkylamino, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, amidine,guanidine, semicarbazone, and imidazole, piperidine, piperazine,4-alkylpiperazine and phenyl optionally substituted with an amino, C₁–C₅alkylamino, C₁–C₆ dialkylamino and lower acylamino optionallysubstituted with one or more amino, lower alkylamino or lowerdialkylamino; and the alkylene chain is optionally substituted with anamino or hydroxyl group; p is independently 0 to 8; and, m is 2 to atleast about
 500. 22. The polymer or oligomer of claim 20, wherein: x andy are NH, z is C═O; A and B are m- or p-phenylene and either (i) A issubstituted at the 2-position with a polar (P) group and B issubstituted at the 5-position with a nonpolar (NP) group, or (ii) A issubstituted at the 5-position with a polar (P) group and B issubstituted at the 2-position with a nonpolar (NP) group, or (iii) A andB are both substituted at the 2-position with a polar (P) group and atthe 5-position with a nonpolar (NP) group, or (iv) A is substituted atthe 2-position with a polar (P) group and at the 5-position with anonpolar (NP) group and B is unsubstituted; NP is a nonpolar groupindependently selected from R⁴ or —U—(CH₂)_(p)—R⁴ wherein R⁴ is selectedfrom the group consisting of hydrogen, methyl, ethyl, n-propyl,iso-propyl, iso-butyl, sec-butyl, tert-butyl, iso-pentyl, andsec-pentyl, and U and p are as defined below; P is a polar groupU—(CH₂)_(p)—V wherein U is absent or selected from the group consistingof O and S and V is selected from the group consisting of amino, loweralkyl amino, lower dialkylamino, imidazole, guanidine, NH(CH₂)_(p)NH₂,N(CH₂CH₂NH₂)₂, piperidine, piperazine, and 4-alkylpiperazine; p isindependently 0 to 8; and m is 2 to at least about
 500. 23. The polymeror oligomer of claim 20, wherein said polymer or oligomer comprises acompound of formula XIV

wherein: R⁴ is selected from the group consisting of methyl, ethyl,n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,n-pentyl, iso-pentyl, and sec-pentyl, and U and p are as defined below;U is absent, O or S and V is selected from the group consisting ofamino, lower alkyl amino, lower dialkylamino, imidazole, guanidine,NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, piperidine, piperazine, and4-alkylpiperazine; p is 0 to 8; and m is 2 to at least about
 30. 24. Thepolymer or oligomer of claim 20, wherein said polymer or oligomercomprises a compound of formula XVII

 wherein: either R¹² and R¹⁴ are independently polar (P) groups and R¹³and R¹⁵ are independently nonpolar (NP) groups substituted at one of theremaining unsubstituted carbon atoms, or R¹² and R¹⁴ are independentlynonpolar (NP) groups and R¹³ and R¹⁵ are independently polar (P) groups;NP is a nonpolar group independently selected from R⁴ or —U—R⁴ whereinR⁴ is selected from the group consisting of methyl, ethyl, n-propyl,iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl,iso-pentyl, and sec-pentyl, and U and p are as defined below; P is apolar group U—(CH₂)_(p)—V wherein U is selected from the groupconsisting of O and S and V is selected from the group consisting ofamino, lower alkyl amino, lower dialkylamino, guanidine, pyridine,piperazine, and 4-alkylpiperazine; p is independently 0 to 8; and m is 2to at least about
 30. 25. A polymer or oligomer comprising a compound offormula XVIII

wherein: x=NH and y=CO; R¹ is (i) -y-C and R² is OH or NH₂ wherein C isselected from the group consisting of C₁–C₆ alkyl, C₁–C₆ haloalkyl,vinyl, 2-propenyl, H-x-(CH₂)_(p)—, (C₁–C₆-alkoxy)C(═O)(CH₂)_(p)—, C₁–C₆alkoxy, benzyloxy, t-butoxy, pyridine and phenyl said pyridine or phenyloptionally substituted with 1 or 2 substituents independently selectedfrom the group consisting of halo, nitro, cyano, C₁–C₆ alkoxy, C₁–C₆alkoxycarbonyl, and benzyloxycarbonyl; or, (ii) is H and R² is-x-(CH₂)_(p)—W wherein x is as defined above and p is as defined belowand W is N-maleimide or V as defined below, or (iii) -y-C and R² isx(CH₂)_(p)—W; or (iv) R¹ and R² together are a single bond; NP is anonpolar group independently selected from R⁴ or —(CH₂)_(p)—R⁴ whereinR⁴ is selected from the group consisting of hydrogen methyl, ethyl,n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,n-pentyl, iso-pentyl, sec-pentyl, and C₁–C₅-haloalkyl, and p is asdefined below; P is a polar group (CH₂)_(p)—V wherein V is selected fromthe group consisting of amino, lower alkyl amino, lower dialkylamino,imidazole, guanidine, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, piperidine,piperazine, and 4-alkylpiperazine; p is independently 0 to 8; and m is 2to at least about
 30. 26. A method of killing microorganisms, saidmethod comprising the steps of: Providing a substrate having disposedthereon a contact killing, facially amphiphilic polymer or oligomer ofclaim 1, claim 14, or claim 20; Placing said facially amphiphilicpolymer or oligomer disposed thereon on said substrate in contact with amicroorganism to allow formation of pores in the cell wall of saidmicroorganism.
 27. The method of claim 26, wherein said substrate isselected from the group consisting of wood, synthetic polymers,plastics, natural and synthetic fibers, cloth, paper, rubber and glass.28. The method of claim 27, wherein said substrate is from a plasticselected from the group consisting of polysulfone, polyacrylate,polyurea, polyethersulfone, polyamide, polycarbonate,polyvinylidenefluoride, polyethylene, polypropylene and cellulosics. 29.A microbiocidal composition comprising a facially amphiphilic polymer oroligomer of claim 1, claim 14, or claim 20 and a solid support selectedfrom the group consisting of wood, synthetic polymers, natural andsynthetic fibers, cloth, paper, rubber and glass.
 30. The microbiocidalcomposition of claim 29, wherein said solid support is a plasticselected from the group consisting of polysulfone, polyacrylate,polyethersulfone, polyamide, polycarbonate, polyvinylidenefluoride,polyethylene, polypropylene and cellulosics.
 31. A method foridentifying a facially amphiphilic polymer or oligomer of claim 1, claim14, or claim 20, said method comprising: (1) selecting a polymer oroligomer backbone or scaffold in which polar (P) and nonpolar (NP)groups can be incorporated; (2) determining parameters for a molecularmechanics force field utilizing ab initio quantum mechanicalcalculations; (3) calculating energetically accessible conformations ofsaid backbone using molecular dynamics or molecular mechanicscalculations; (4) identifying energetically accessible conformations ofsaid backbone wherein the periodicity of a geometrical/conformationalrepeat matches a sequence repeat; (5) synthesizing monomers with polarand nonpolar substituents; (6) synthesizing an antimicrobial polymer oroligomer containing said monomers by solution or solid-phase synthesis.32. A process for producing an antimicrobial surface by attaching anantimicrobial facially amphiphilic polymer or oligomer of claim 1, claim14, or claim 20 to a surface, said process comprising treating saidsurface with a first chemically reactive group and reacting said polymeror oligomer linked to a second reactive group thereto.
 33. The processof claim 32, wherein said first reactive group is a1-(trialkoxysilyl)propylamine and said second reactive group is anactivated carboxylic acid.
 34. The process of claim 32, wherein saidfirst reactive group is a ω-(trialkoxysilyl)alkyl bromomethylacetamideand said second reactive group is a thiol.
 35. The process of claim 32,wherein said first reactive group is a N-[ω-(trialkoxysilyl)alkyl]maleimide and said second reactive group is a thiol.
 36. The process ofclaim 32, wherein said first reactive group is a gold surface and saidsecond reactive group is a thiol.
 37. An antimicrobial compositioncomprising a facially amphiphilic polymer or oligomer of claim 1, claim14, or claim 20 and a composition selected from the group consisting ofpaint, coatings, lacquer, varnish, caulk, grout, adhesives, resins,films, cosmetics, soap and detergent.
 38. An improved catheter, saidimprovement comprising incorporating or attaching an antimicrobialfacially amphiphilic polymer or oligomer of claim 1, claim 14, or claim20 therein or thereto.
 39. An improved contact lens, said improvementcomprising incorporating or attaching an antimicrobial faciallyamphiphilic polymer or oligomer of claim 1, claim 14, or claim 20therein or thereto.
 40. An improved plastic device for the hospital andlaboratory, said improvement comprising incorporating or attaching anantimicrobial facially amphiphilic polymer or oligomer of claim 1, claim14, or claim 20 therein or thereto.
 41. An improved woven and nonwovenfabric for hospital use, said improvement comprising incorporating orattaching an antimicrobial facially amphiphilic polymer or oligomer ofclaim 1, claim 14, or claim 20 therein or thereto.
 42. A microbiocidalcomposition comprising a facially amphiphilic polymer or oligomer ofclaim 1, claim 14, or claim 20 and a medical device or medical product.43. The microbiocidal composition of claim 42, wherein the medicaldevice or medical product is selected from the group consisting ofsurgical gloves, implanted devices, sutures, catheters, dialysismembranes, and water filters and implements.
 44. A microbiocidalcomposition comprising a facially amphiphilic polymer or oligomer ofclaim 1, claim 14, or claim 20 and a material comprising spinnablefibers.
 45. The microbiocial composition of claim 44, wherein thematerial comprising spinnable fibers is selected from the groupconsisting of fabrics, surgical gowns, and carpets.